WO2011055247A1

WO2011055247A1 - A synthetic cyclic dipeptide and a process thereof

Info

Publication number: WO2011055247A1
Application number: PCT/IB2010/054533
Authority: WO
Inventors: Thimmaiah Govindaraju
Original assignee: Jawaharlal Nehru Centre For Advanced Scientific Research
Priority date: 2009-11-09
Filing date: 2010-10-07
Publication date: 2011-05-12

Abstract

The disclosure relates to preparation and self-assembly of aromatic cyclic dipeptide into one and two dimensional nano, meso and micro structures. The said structures of cyclic dipeptide can be electrospinned into threads, fabrics, suture, bandage materials. They are also useful in cell culturing, tissue culturing, drug delivery system, as composite materials, as inhibitors of fibrillization and in Biomedical research such as neurological regeneration and organ replacement studies.

Description

A SYNTHETIC CYCLIC DIPEPTIDE AND A PROCESS THEREOF

TECHNICAL FIELD

The present disclosure is in relation to peptide and nanotechnology, in particular to nano, meso and microstructures of cyclic dipeptide. The disclosure provides supramolecular self-assembling cyclic dipeptides, its characteristics and a process for its preparation.

BACKGROUND

Biomolecules such as polypeptides, proteins, carbohydrates and lipids are the building blocks of a range of biological materials. These materials have essential biological functions such as structural stability, mechanical (cyto skeletal) strength, self-defense, and many other physiological functions. An actively pursued area of research today involves the design of small organic molecules and peptides which self-assemble to form well defined nano and meso structures with properties similar to natural materials. In particular, self-assembling peptides can play an important role in the area of biomaterials as substitutes for materials of biological origin. This is primarily due to the fact that peptides are modular in nature, and their structure and physico-chemical properties can be tuned by chemical modifications to suit a desired application. Biomaterials play an important role in years to come owing to their capability to replace various materials of biological origin which are difficult to obtain in large quantities and also find profound usage in biomedicine. In particular peptide based biomaterials are of great interest due to their easy access through well established peptide synthesis protocols. Biomolecules such as peptides and proteins are responsible for whole lot biological materials ranging from spider silk, collagen, actin and keratin.

Peptide based materials find applications as biomaterials in cell culture, tissue engineering, stem cell growth, drug delivery and in the form of composite materials. In recent years, a number of nanostructures formed by cyclic and acyclic peptides have been reported. These cyclic dipeptides are known to form various self-assembled structures such as microcapsules, nanotubes, nanofibers and nanotapes and offer higher stability compare to their acyclic congeners. While the formation of two dimensional (2D) nanosheets by non-peptidic molecules such as metallo-porphyrin and fullerene (C₆o) has been reported recently, aggregation of a cyclic or acyclic peptide into nano and mesosheets with a large lateral surface has not been observed.

Peptide and proteins based fibril formations have also been implicated in various human diseases such Alzheimer's, Parkinson's, type II diabetes, and Prion disease etc. For example β-amyloid peptide undergoes fibrillization that results in the formation of aggregated fibers leading to Alzheimer's disease. Accordingly, this aspect of β-amyloid peptide fibrillization to form fiber aggregates responsible for Alzheimer disease became inspiration to many researchers working on the designing of self-assembled peptide based biomaterials. Designing small organic molecules and peptides which self-assemble to form fibers and fiber bundles with properties comparable to natural fibers is of prime importance in the area of material science. It is utmost important to study the formation of these peptide fibrils and the advantage is of threefold, 1) provides insight into the molecular mechanism underlying state of fibrillization that form fiber aggregates which main cause of the disease itself, 2) developing potential inhibitors to dissolve the fiber aggregates, and 3) discovering artificial peptide based biomaterials which can mimic biological materials. STATEMENT OF THE DISCLOSURE

Accordingly, the present disclosure is in relation to a synthetic cyclic dipeptide which self assembles to form nano, meso and micro structures; a self assembled nano, meso and micro structure of synthetic cyclic dipeptide; a process for preparation of cyclic dipeptide, the process comprising steps of - a) condensing fluorenylmethyloxycarbonyl protected amino acid with an ester using coupling reagent to obtain protected dipeptide and b) deprotecting the protected dipeptide to obtain the cyclic dipeptide; a process for preparation of nano, meso and micro structures of cyclic dipeptide, the process comprising steps of - a) condensing fluorenylmethyloxycarbonyl protected amino acid with an ester using coupling reagent to obtain protected dipeptide; and b) deprotecting the protected dipeptide followed by solvent evaporation or filtration to obtain the nano, meso and micro structures of the cyclic dipeptide; a composition comprising a synthetic cyclic dipeptide which self assembles to form nano, meso and micro structures along with additives; a composition comprising self assembled nano, meso and micro structure of synthetic cyclic dipeptide along with additives; a method of inhibiting fibrillization in neurodegenerative diseases, the method comprising act of contacting self assembled structure, along with pharmaceutically acceptable additives in a subject in need thereof; a method of cell culturing, the method comprising act of culturing cells in a nutrient medium along with meso and micro structures as template for differentiation of cells; a method of using nano, meso and micro structures as optoelectronic component, the method comprising act of contacting the nano, meso and micro structure with an electronic device in need thereof; a method of drug delivery, the method comprising act of delivering a predetermined drug in an envelop of nano, meso and micro structure; and a method of using nano, meso, and micro structure as a biomaterial, the method comprising act of contacting the nano, meso and micro structure along with additives in a subject in need thereof.

BRIEF DESCRIPTION OF ACCOMPANYING FIGURES

In order that the disclosure may be readily understood and put into practical effect, reference will now be made to exemplary embodiments as illustrated with reference to the accompanying figures. The figure together with a detailed description below, are incorporated in and form part of the specification, and serve to further illustrate the embodiments and explain various principles and advantages, in accordance with the present disclosure where:

Figure 1 shows (a) Molecular structure of cyclic dipeptide.

Figure 2 shows self-assembled peptide fiber bundles.

Figure 2A shows FESEM images of CDP 1 (35',65)-3,6-dibenzylpiperazine-2,5-dione) suspended in dichloromethane.

(a) Dimensions of fiber bundles.

(b) Insights of fiber bundles showing self assembly.

(c) Micrometer thick solid fiber bundle.

(d) Individual fiber bundle milled using ion beam. Figure 2B (e) & (f) shows HR-TEM images of CDP l(3S,6S)-3,6-dibenzylpiperazine- 2,5-dione) suspended in dichloro methane.

Figure 3A & B shows HRTEM images of self-assembled cyclic dipeptide fiber bundles.

Figure 4A shows FESEM images of self-assembled cyclic dipeptide fiber bundles formed from the solutions of CDP l(35',65)-3,6-dibenzylpiperazine~2,5-dione) in dichloromethane with acetic acid.

Figure 4B shows FESEM images of self-assembled cyclic dipeptide fiber bundles formed from the solutions of CDP l(35',65)-3,6-dibenzylpiperazine-2,5-dione) in dichloromethane with acetic acid.

Figure 5 shows HR-TEM images of fiber bundles.

Figure 5A shows fiber bundles formed from the solution of CDP l(3S,6S)-3,6- dibenzylpiperazine-2,5-dione) in 1 ,1,1 ,3,3,3-hexafluoroisoporpanol (HFP). The inset is expanded view of the selected region of a fiber bundle (square)

Figure 5B shows the nanofibers projecting out at the ends of a fiber bundles.

Figure 6A [a,b] fiber bundles vials showing gelation property of CDP l(3S,6S)-3,6- dibenzylpiperazine-2,5-dione).

Figure 6B [c, d, e and f| shows FESEM images of CDP l(35,6S)-3,6- dibenzylpiperazine-2,5-dione) from vials 1-4 to show the topographical changes.

Figure 7 shows thermogravimtric analysis (TGA) of A) CDP \(3S,6S)-3,6- dibenzylpiperazine-2,5-dione) fiber bundles (solid), B) CDP 1 fiber bundles suspended in chloroform (CHC1₃), C) CDP 1-vial 1, D) CDP 1-vial 2, E) CDP 1-vial 3, F) CDP 1-vial 4. [Vials 1-4, Refer Figure 6]. Thermal transitions observed- A) 324.5 °C and 390.8°C, B) 314.9°C, C) 242.4 °C, 295.2°C, D) 302.3 °C and 321.6°C, E) 227.49 °C, 297.6 °C, and 342.4°C and F) no clear transition observed. Figure 8 shows FESEM (a) and HRTEM (b) micrographs of cyclic Phenylglycinylphenylglycine [(35',65 -3,6-diphenylpiperazine-2,5-dione or cyclic (L- Phg-Z-Phg)] mesosheets suspended in methanol. FESEM (c) and HRTEM (d) micrographs of nanosheets formed by the solution of Phenylglycinylphenylglycine in CHCI₃-TFA. Inset (b): high resolution TEM image of 2D mesosheet showing layered structure. Inset (d): high resolution image of nanosheets showing smooth layer surface.

Figure 9 shows thermo gravimetric analysis (TGA) of

2,5-dione 2D mesosheets (solid). The weight losses were determined by first derivative (DTG, red) curve. Main transitions observed are 220.9 and 310.1 °C, an indication of existence of self-organized structural hierarchy (nanosheets and mesosheets) and the presence of molecular-chains. The 2D mesosheets are found to be stable up to 325 °C.

Figure 10 shows (a) AFM image of 2D mesosheet of

2,5-dione, (b) 3D view of 2D mesosheet and (c) height profile of 2D mesosheet (-300 nm).

Figure 11 shows Star-shaped patterns. FESEM images of cyclic (3S,6S)-3,6- diphenylpiperazine-2,5-dione in 1,1 ,1,3,3,3-hexafiuoroisoporpanol (HFP) a) star-shaped pattern, b) high resolution image of star branch edge, c) HRTEM image of star-shaped patterns formed by (35',65)-3,6-diphenylpiperazine-2,5-dione in HFP and high resolution image of self-organized nanosheets at the star branch edge (d). AFM image of star- shaped patterns formed by (35',65)-3,6-diphenylpiperazine-2,5-dione in HFP (e) and high resolution AFM image of 2D nanosheets at star branch edge and corresponding height profile (f). The height profile show the presence of 2D nanosheets of uniform thickness (height a = b~30 nm) which are the building units of star-shaped patterns.

Figure 12 shows FESEM micrographs of 2D mesosheets (which also includes rhomboid shape) of (35',65 -3,6-diphenylpiperazine-2,5-dione suspended in methanol (a) and (b). Mesosheet shape shows that adjacent sides are of different length (c) and (d). FESEM micrograph of an incompletely grown 2D mesosheet shows the self-organizing nanosheets on surface (e) and (f), red arrow pointing to the self-organizing nanosheets. Figure 13 shows HRTEM micrographs of (35',65)-3,6-diphenylpiperazine-2,5-dione mesosheets (a) and (b) High resolution images (c) and (d), reveal the layered structure of mesosheets. Figure 14 shows FESEM micrographs of 2D nanosheets formed from the solutions of (3S,6S)-3,6-diphenylpiperazine-2,5-dione in CHC1₃-TFA (a) and CH₂C1₂-TFA (b) HRTEM micrographs of 2D nanosheets formed from the solutions of (3S,6S)-3,6- diphenylpiperazine-2,5-dione [cyclic (Phg-Phg)] in CHCI3-TFA (c) and CH₂C1₂-TFA (d). Figure 15 shows AFM image of 2D nanosheets formed from the solution of (3S,6S)-3,6- diphenylpiperazine-2,5-dione in CHCI3-TFA and corresponding height profiles. Average topographical layer-thickness ~60 nm.

Figure 16 shows (a) FESEM micrograph of 2D rhomboid sheets of (3i?,65)-3,6- diphenylpiperazine-2,5-dione [cyclic D-Phg-Z-Phg)] suspended in methanol, (b) HRTEM micrograph of (3i?,65)-3,6-diphenylpiperazine-2,5-dione suspended in methanol, (c) AFM image of rhomboid 2D sheets, inset show the height profile (~ 200 nm). (d) high resolution image of the 2D sheet edge show the existence layered hierarchy, (e) FESEM micrograph of flowers formed by the solution of (3i?,65)-3,6- diphenylpiperazine-2,5-dione in chloroform-TFA. (f) high resolution images of nanosheets formed by the solution of (3i?,65)-3,6-diphenylpiperazine-2,5-dione in chloroform-TFA. These nanosheets form aggregates (flowers) as result of diffusion- limited solvent evaporation. Figure 17 shows NMR characterization of the 2D sheets of (3S,6S)-3,6- diphenylpiperazine-2,5-dione. (a) ID ^!H and (b) 2D [¹⁵N,^!H] HSQC spectra acquired in the solution state at different additions of TFA. Chemical shift assignments of peaks are indicated. Spectra/peaks marked i-v in (a) and (b) indicate 0, 1, 2, 3 and 5 additions of TFA respectively, (c) 1H-¹³C CP and (d) 2D 1H-¹³C HETCOR spectra acquired in the solid state at a MAS rate of 11 k Hz. Figure 18 shows the hierarchy in the spontaneous formation of 2D sheets involves the self-assembly of cyclic Phenylglycinylphenylglycine [cyclic (Phg-Phg)] to 2D nanosheets, followed by self-organization of these nanosheets to form 2D mesosheets resembling the layered structure. Solution of Phenylglycinylphenylglycine [cyclic (Phg- Phg)] in CHCI₃ -TFA and CH₂CI₂ -TFA on solvent evaporation form nanosheets. In fluorinated solvent (HFP) star-shaped patterns formed as a result of diffusion controlled aggregation of nanosheets.

Figure 19 shows plot of amide temperature coefficient at different additions of TFA. The first point (0 μί) corresponds to a suspension of mesosheets in CDCI₃. The temperature coefficient could not be measured at 1 μΐ. of TFA due to overlap of ^!H^N signal with those of aromatic ^!H.

Figure 20 shows plot of a region of 2D [1H, ^!H] ROESY spectrum illustrating the cross peaks due to chemical exchange between the ^!H^N (amide) of (3S,6S)-3,6- diphenylpiperazine-2,5-dione and TFA (-COOH proton) at 5μL addition of TFA to a sample containing mesosheets in CDCI₃. The chemical exchange peaks and the amide temperature coefficients together suggest the disruption of intermolecular hydrogen bond in the mesosheets and interaction of TFA with monomeric (3S,6S)-3,6- diphenylpiperazine-2,5-dione.

Figure 21 shows Thermogravimetric analysis (TGA) of (3i?,65 -3,6-diphenylpiperazine- 2,5-dione [cyclic D-Phg-Z-Phg)] 2D mesosheets (solid). The weight losses were determined by first derivative (DTG, red) curve. Main transitions observed are 306.9 and 497.3 °C, an indication of existence of self-organized structural hierarchy (nanosheets and mesosheets). The 2D mesosheets are found to be stable up to 500 °C. High thermal stability is attributed to the presence of molecular-layers.

Figure 22 shows Transformation self-assembled 2D mesosheets of cyclic (Z⁾-Phg-Z-Phg) into crystals (diamondoid) in methanol after 2 months, (a) FESEM, (b) HRTEM and (c) AFM images show the formation cyclic (Z⁾-Phg-Z-Phg) crystallites on the surface of self- assembly based 2D mesosheets. The crystallization occurs in precise pattern (c and d, inset) AFM height profile showing the thinning of 2D mesosheets as the crystallization process initiates on its surface (2D sheet thickness -120 nm, thickness of crystallites ~ 64 nm).

Figure 23 shows crystallization studies (a) Rhomboid single-crystalline 2D sheets of cyclic (Z⁾-Phg-Z-Phg) formed in 2-methoxyethanol. The shape of these crystals is similar to that of rhomboid 2D mesosheets formed by self-assembly based aggregation, (b) Optical profiler image, (c) Optical profiler analysis. The size of the rhomboid crystalline sheets is relatively larger compare to 2D mesosheets (lateral dimension > 600 μηι). The height of crystalline sheet was found to be ~ 300 μηι. Scale bar: 350 μηι (d) crystal packing of cyclic (Z⁾-Phg-Z-Phg) into molecular-layers.

DETAILED DESCRIPTION

The present disclosure relates to a synthetic cyclic dipeptide which self assembles to form nano, meso and micro structures.

In an embodiment of the present disclosure, dipeptide is obtained from amino acids with stereochemistry selected from a group comprising (R,R), (S,S), (R,S) and (S,R).

In another embodiment of the present disclosure, the dipeptide is obtained from amino acids selected from a group comprising natural aromatic amino acids, unnatural aromatic amino acids, derivatives of amino acids and any combination thereof.

In yet another embodiment of the present disclosure, the amino acids are selected from a group comprising Phenylalanine, Phenylglycine and combination thereof.

In still another embodiment of the present disclosure, the dipeptide is 3,6- dibenzylpiperazine.

In still another embodiment of the present disclosure, the dipeptide is 3,6- dibenzylpiperazine-2-5-dione.

In still another embodiment of the present disclosure, the dipeptide is 3,6- diphenylpiper azine .

In still another embodiment of the present disclosure, the dipeptide is 3,6- diphenylpiperazine-2,5-dione. The present disclosure relates to a self assembled nano, meso and micro structure of synthetic cyclic dipeptide.

In an embodiment of the present disclosure, the dipeptide is 3,6-dibenzylpiperazine. In another embodiment of the present disclosure, the dipeptide is 3,6-dibenzylpiperazine- 2-5-dione.

In yet another embodiment of the present disclosure, the dipeptide is 3,6- diphenylpiper azine .

In still another embodiment of the present disclosure, the dipeptide is 3,6- diphenylpiperazine-2,5-dione.

In still another embodiment of the present disclosure, the nano, meso and micro structure is selected from a group comprising nanofibers, nanofiber bundles, fibers, fiber bundles, nanotubes, nanotube bundles, nanosheets, mesosheets, 2D sheets and gels.

In still another embodiment of the present disclosure, the meso and 2D sheets have layered hierarchy.

The present disclosure relates to a process for preparation of cyclic dipeptide, the process comprising steps of:

a) condensing fluorenylmethyloxycarbonyl protected amino acid with an ester using coupling reagent to obtain protected dipeptide; and

b) deprotecting the protected dipeptide to obtain the cyclic dipeptide.

The present disclosure relates to a process for preparation of nano, meso and micro structures of cyclic dipeptide, the process comprising steps of:

b) deprotecting the protected dipeptide followed by solvent evaporation or filtration to obtain the nano, meso and micro structures of the cyclic dipeptide.

In an embodiment of the present disclosure, the preparation is carried out at a temperature ranging from about 0°C to about 50°C, preferably about 25°C.

In another embodiment of the present disclosure, the ester is amino acid ester.

In yet another embodiment of the present disclosure, the amino acid is selected from a group comprising natural aromatic amino acid, unnatural aromatic amino acid, derivates of amino acids and any combination thereof, with stereochemistry selected from a group comprising (R,R), (S,S), (R,S) and (S,R).

In still another embodiment of the present disclosure, the condensing reaction is carried out for a time period ranging from about 1 h to about 12 h, preferably about 5 h.

In still another embodiment of the present disclosure, the coupling reagent is selected from a group comprising l-Ethyl-3-(3-dimethylaminopropyl) carbodiimide, 1- hydroxybenzotriazole, Diisopropylehtylamine, 0-( 1 H-benzotriazole- 1 -yl)-N,N,N',N'- tetramethyluronium hexafluorophosphate, 0-( 1 H-benzotriazole- 1 -yl)-N,N,N',N'- tetramethyluronium tetrafiuoroborate, Dicyclohexylcarbodiimide, diisopropylcarbodiimide, (Benzotriazol- 1 -yloxy)tris(dimethylamino)phosphonium hexafluorophosphate, 0-(7-Azabenzotriazol-l-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, 0-(6-Chlorobenzotriazol-l-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, 0-(3,4-Dihydro-4-oxo-l,2,3-benzotriazine-3-yl)-N,N,N',N'- tetramethyluronium tetrafiuoroborate, benzotriazol- 1 -yl-oxytripyrrolidinophosphonium hexafluorophosphate and Carbonyldiimidazole.

In still another embodiment of the present disclosure, the deprotection is achieved using a base at a concentration ranging from about 1 % to about 100 %, preferably about 10 % in a solvent for a time period ranging from about 0.5 h to about 24 h, preferably for about 2 h.

In still another embodiment of the present disclosure, the base is selected from a group comprising piperidine, ammonia, morpholine, sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium hydride, n-butyl lithium, sodium amide, piperidine, ammonia and morpholine.

In still another embodiment of the present disclosure, the solvent is an organic solvent selected from a group comprising dichloromethane, dimethylformamide, acetonitrile and toluene.

In still another embodiment of the present disclosure, the dipeptide is 3,6- dibenzylpiperazine .

In still another embodiment of the present disclosure, the dipeptide is 3,6- dibenzylpiperazine-2-5-dione. In still another embodiment of the present disclosure, the dipeptide is 3,6- diphenylpiper azine .

In still another embodiment of the present disclosure, the meso and micro structure are formed by self assembly of nano structures.

In still another embodiment of the present disclosure, the nano, meso and microstructures are crystalline or non-crystalline in nature.

In still another embodiment of the present disclosure, the meso and micro structure are soluble in solvents selected from a group comprising acidified organic solvents and fluorinated solvents.

In still another embodiment of the present disclosure, the organic solvents are selected from a group comprising dichloromethane, chloroform, ethylacetate, cyclohexane, hexane, toluene, dimethylformamide and dimethylsulfoxide; and the fluorinated solvents are selected from a group comprising hexafluoroisopropanol and tetrafiuorethanol.

In still another embodiment of the present disclosure, solution of the meso and micro structure in a solvent form suspension or gel upon acidification.

In still another embodiment of the present disclosure, the solution has a concentration of about 0.25 mg/ml to about 50 mg/ml, preferably about 2.5 mg/ml.

In still another embodiment of the present disclosure, the acidification is carried out by an organic acid.

In still another embodiment of the present disclosure, the organic acid is selected from a group comprising acetic acid, formic acid, trichloroacetic acid, dichloroacetic acid and trifluroacetic acid, preferably trifiuroacetic acid.

In still another embodiment of the present disclosure, the suspension is formed at an acid volume of about 2.5 μΐ to about 6.5 μΐ, and the gel is formed at an acid volume of about 11 μΐ to about 13 μΐ, preferably about 12 μΐ . In still another embodiment of the present disclosure, the solution of meso and micro structure form nanostructures selected from a group comprising nanofibers, fibers, nanotubes and nanosheets.

The present disclosure relates to a composition comprising a synthetic cyclic dipeptide which self assembles to form nano, meso and micro structures along with additives.

The present disclosure relates to a composition comprising self assembled nano, meso and micro structure of synthetic cyclic dipeptide along with additives.

In an embodiment of the present disclosure, the dipeptide is obtained from a group comprising natural aromatic amino acids, unnatural aromatic amino acids, derivatives of amino acids and any combination thereof.

In another embodiment of the present disclosure, the amino acids are selected from a group comprising Phenylalanine, Phenylglycine and combination thereof.

In yet another embodiment of the present disclosure, the dipeptide is 3,6- dibenzylpiperazine .

In still another embodiment of the present disclosure, the dipeptide is 3,6- dibenzylpiperazine-2-5-dione

In still another embodiment of the present disclosure, the additives are selected from a group comprising binders, disintegrants, diluents, lubricants, plastizers, permeation enhancers, solubilizers, preservatives, colouring agents, oxidizing agens, reducing agenets, pharmaceutical agents, nanoparticles, silica, hydroxyapatite, metal compositions, polymers, fibers and natural materials.

The present disclosure relates to a method of inhibiting fibrillization in neurodegenerative diseases, the method comprising act of contacting self assembled structure, along with pharmaceutically acceptable additives in a subject in need thereof. The present disclosure relates to a method of cell culturing, the method comprising act of culturing cells in a nutrient medium along with meso and micro structures as template for differentiation of cells.

The present disclosure relates to a method of using nano, meso and micro structures as optoelectronic component, the method comprising act of contacting the nano, meso and micro structure with an electronic device in need thereof.

The present disclosure relates to a method of drug delivery, the method comprising act of delivering a predetermined drug in an envelop of nano, meso and micro structure.

The present disclosure relates to a method of using nano, meso, and micro structure as a biomaterial, the method comprising act of contacting the nano, meso and micro structure along with additives in a subject in need thereof.

In an embodiment of the present disclosure, the biomaterial is selected from a group comprising composites, suture, fabric and bandage material. An embodiment of the present disclosure relates to the preparation of synthetic cyclic peptides using the solution phase synthesis protocol. This peptide synthesis is followed by the self-assembling stage to give rise to higher order structures. Initially, the protected amino acid and the amino acid ester are prepared by conventionally known protocols. This is followed by the condensation of the protected amino acid with the amino acid ester using coupling reagents. The protected peptide obtained by the condensation step is subjected to deprotection using deprotecting agents, followed by filtration to obtain the cyclic peptide. These cyclic peptides, preferably cyclic dipeptides spontaneously self assemble to give rise to higher order structures. In an embodiment of the present disclosure, the condensation step is carried out for a time duration of about 1 hour to about 12 hours, making use of coupling reagents such as 1- Ethyl-3-(3-dimethylaminopropyl) carbodiimide, 1 -hydroxybenzotriazole,

Diisopropylehtylamine, 0-(lH-benzotriazole-l-yl)-N,N,N',N'-tetramethyluronium hexafiuorophosphate, 0-( 1 H-benzotriazole- 1 -yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, Dicyclohexylcarbodiimide, diisopropylcarbodiimide, (Benzotriazol-1- yloxy)tris(dimethylamino)phosphonium hexafiuorophosphate, 0-(7-Azabenzotriazol- 1 - yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate , 0-(6-Chlorobenzotriazol-l-yl)- Ν,Ν,Ν',Ν'-tetramethyluronium hexafluorophosphate, 0-(3,4-Dihydro-4-oxo-l ,2,3- benzotriazine-3-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, benzotriazol- 1 -yl- oxytripyrrolidinophosphonium hexafluorophosphate and Carbonyldiimidazole.

In another embodiment of the present disclosure, the protected dipeptide is deprotected using deprotecting agents such as Dichloromethane or Piperidine in a solvent, at a concentration of about 1 % to about 100 %, for time duration of about 30 minutes to about 24 hours.

In an embodiment of the present disclosure, the deprotected peptide spontaneously self- assemble to form nano, meso, and macrostructures namely nanofibers nanofiber bundles, fiber bundles, nanotubes, nanotube bundles, nanosheets, mesosheets and gels.

In an embodiment of the present disclosure, all the solvents and reagents are obtained from Sigma- Aldrich and used as received unless otherwise mentioned. 1H and ¹³C NMR spectra are measured on a Bruker AV-400 spectrometer with chemical shifts reported as ppm. Field emission scanning electron microscopy (FESEM) measurements are performed by using an FESEM, FEI Quanta 3D FEG microscope or FESEM, FEI Nova nanoSEM-600 equipped with field emission gun operating at 30 kV. High resolution transmission electron microscopy (HRTEM) micrographs are obtained (on a 200 mesh holey carbon supported copper grid) with JEOL JEM 3010 electron microscope operating at 300 kV. Atomic force microscopy (AFM) measurements are performed using Innova (Veeco) atomic force microscope. In an embodiment the instant disclosure provides cyclic dipeptides which self-assemble to produce nanofibers and fiber bundles that resemble natural fibers such as collagen and spider silk. Simplest and straight forward synthetic route to access the cyclic dipeptides is disclosed. The characterization techniques and the corresponding data prove that the instant cyclic dipeptides are capable of forming fibers and fiber bundles which mimic natural fibers. The cyclic dipeptide based meso structures, nano structures and fiber bundles reported in this disclosure are distinct. In an embodiment, the present disclosure, provides for cyclic dipeptides such as Phenylalanylphenylalanine (Phe-Phe), Phenylglycinylphenylglycine (Phg-Phg).

In an embodiment, the present study demonstrates that the simplest aromatic cyclic Phenylglycinylphenylglycine (Phg-Phg) dipeptide form well defined 2D nano and mesosheets with large lateral dimensions. The self-assembly begins by formation of 2D nanosheets, followed by self-organization of these nanosheets to form 2D mesosheets resembling the layered structure of graphene. This is in contrast to its acyclic congener, which has been shown to form nanospheres. Highlight of this work is the large scale production of 2D sheets from the smallest cyclic dipeptide which in turn can be obtained by a simple and straight forward synthetic route.

In an embodiment, the present disclosure also relates to the formation of 2D nano and mesosheets from cyclic Phenylglycinylphenylglycine dipeptide (Phg-Phg) spanning several micrometers in lateral dimensions. The structural morphologies of the 2D sheets are being extensively characterized using different microscopy techniques such as field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM) and atomic force microscopy (AFM) and by solution/solid-state NMR spectroscopy. Further, it is observed that their hierarchy and morphology resemble that of graphene.

The present invention is further elaborated by the following examples and figures. However, these examples should not be construed to limit the scope of the invention. Example 1: Synthesis of Cyclic dipeptide: Cyclic Phenylalanylphenylalanine [(3,6- dibenzylpiperazine-2-5-dione) or cyclic (Phe-Phe)].

The synthesis of Cyclic dipeptide involves the following 2 steps.

Step I: Synthesis of protected Dipeptide

9-fluorenylmethoxycarbonyl (Fmoc)-phenylalanine (Fmoc-Phe-OH) and phenylalanine methyl ester (H-Phe-OMe) are prepared using standard protection methods. Fmoc protected L/D-phenylalanylphenylalanine methylester (Fmoc-Phe-Phe-OMe) is prepared by standard peptide coupling procedure. Fmoc-Phe-OH (2 g, 5.16 mmol) is dissolved in dichloromethane, H-Phe-OMe (1.23 g, 5.67 mmol), l-ethyl-3-(3- dimethylaminopropyl)carbodiimide (EDC.HC1, 1.19 g, 6.19 mmol), 1- hydroxybenzotriazole and (HOBt, 1.2 g, 6.19) are added. The solution is cooled to ice temperature. Diisopropylethylamine (DIPEA, 2.14, 16.51 mmol) is added and the reaction mixture is stirred at ice temperature for 1 h and then at room temperature for 5 h. The reaction progress is monitored by thin layer chromatography (TLC). Reaction mixture is evaporated to dryness and extracted from dichloromethane, washed with water, dried over anhydrous sodium sulfate. The solvent is evaporated to obtain Fmoc- Phe-Phe-OMe in quantitative yield.

Step II: Synthesis of (3S,6S)-3,6-dibenzylpiperazine-2,5-dione (CDP 1)

The dipeptide Fmoc-Phe-Phe-OMe from the previous step, example 1 (1 g, 1.82 moles) is subjected to Fmoc-deprotection in 10% piperidine/dichloromethane for 2 h. The reaction mixture is evaporated to dryness and the residue is re-dissolved into dichloromethane. The cyclic dipeptide (CDP 1) spontaneously forms insoluble fiber bundles in dichloromethane. The suspension is filtered, washed with dichloromethane and methanol and dried to obtain CDP 1 in quantitative yield. Relevant NMR data is provided herewith: 1H NMR (CDCI₃-CF₃COOH, 400 MHz) δ_Η 2.15-2.25 (2H, Q), 2.9-3.15 (2H, dd), 4.25- 4.40 (2H, t), 7.00-7.10 (2H, d), 7.30-7.45 (5H, m); ¹³C NMR (CDCI₃-CF₃COOH, 400 MHz) (5c 39.7, 56.3, 128.4, 129.4, 129.8, 133.5, 170.0; Anal. Calcd (%) for Ci₈Hi₈N₂0₂ Found: C, 73.43; H, 6.19; N, 9.48; O, 10.90. Expected: C, 73.45; H, 6.16; N, 9.52; O, 10.87; GCMS: 294 [M⁺].

Synthesis of cyclic Phenylalanylphenylalanine [(3S,65)-3,6-dibenzylpiperazine-2,5- dione (CDP 1) or cyclic (Phe-Phe)]

It is achieved through a robust and straight forward synthetic route developed as shown in Scheme 1. 9-Fluorenylmethyloxycarbonyl (Fmoc)- protected phenylalanine (Fmoc-Phe- OH) was condensed with phenylalanine methylester (H-Phe-OMe) using standard peptide coupling reagents to give the protected dipeptide Fmoc-Phe-Phe-OMe. The Fmoc-Phe- Phe-OMe is subjected to Fmoc-deprotection with 10% piperdine in dichloromethane. During this deprotection process the dipeptide methylester undergo cyclization to give Cyclic Dipeptide in quantitative yield.

Similarly other isomers are synthesized following the above described procedure.

Disclosed here is the simplest and cost effective synthetic procedure for the synthesis of Cyclic Dipeptide, as depicted in scheme 1. Highlight of the synthetic method disclosed here is that no tedious purification procedures involved which are very common in organic synthesis. Since the cyclic dipeptide spontaneously self-assemble to give insoluble fiber bundles, simple filtration is enough to obtain the Cyclic Dipeptide as fiber bundles in its highest purity.

Example 2: Self Assembly of cyclic Phenylalanylphenylalanine [(3S,6S)-3,6- dibenzylpiperazine-2,5-dione (CDP 1) or cyclic (Phe-Phe)]

Cyclic Dipeptides (Scheme 1) spontaneously self-assemble to fibers bundles of several millimeter long and thickness ranging from nano to micrometer. There are at least two to three level of supramolecular self-assembly process is towards the formation of fiber bundles. Cyclic Dipeptide self-assemble to form nanofibers which again self-assemble to nano fiber bundles of several hundred nanometer thickness. These nanofiber bundles further undergo self-assembly to produce fiber bundles of millimeter long and micrometer thick. This is very much the mimic of biological processes involved in the production of natural fibers such as spider silk, collagen etc. Cyclic Dipeptide once assemble into fiber bundles, insoluble in most of the organic solvents including methanol and water. Efforts towards making Cyclic Dipeptide fibers soluble in organic solvents lead to the gain of invaluable information about their material structure and topography, which will be discussed later.

Example 3: Synthesis of Cyclic dipeptide: Cyclic Phenylglycinylphenylglycine [(3,6- diphenylpiperazine-2,5-dione) or cyclic (L-Phg-L-Phg)]

The synthesis of cyclic dipeptide involves the following 2 steps. Step I: Synthesis of protected Dipeptide

9-Fluorenylmethoxycarbonyl (Fmoc)-L-phenylglycine (Fmoc-Phg-OH) and L- phenylglycine methyl ester (H-Phg-OMe) are prepared by using standard protection protocols. Fmoc protected L-phenylglycinylphenylglycine methylester (Fmoc-Phg-Phg- OMe) is prepared by peptide coupling procedure. Fmoc-Phg-OH (2 g, 5.16 mmol) is dissolved in dichloromethane, H-Phg-OMe (1.23 g, 5.67 mmol), l-ethyl-3-(3- dimethylaminopropyl) carbodiimide (EDC.HC1, 1.19 g, 6.19 mmol), 1- hydroxybenzotriazole and (HOBt, 1.2 g, 6.19 mmol) are added. The solution is cooled to ice temperature. Diisopropylethylamine (DIPEA, 2.14 g, 16.51 mmol) is added and the reaction mixture is stirred at ice temperature for 1 h and then at room temperature for 5 h. The reaction progress is monitored by thin layer chromatography (TLC). Reaction mixture is evaporated to dryness and extracted from dichloromethane, washed with water, dried over anhydrous sodium sulfate. The solvent is evaporated to obtain Fmoc- Phg-Phg-OMe in quantitative yield. The cyclic dipeptide Phenylglycinylphenylglycine shown in Figure 1 was prepared by coupling Fmoc-Phg-OH with Phg-OMe using peptide coupling reagents. The protected dipeptide (Fmoc-Phg-Phg-OMe) under Fmoc- deprotection conditions resulted in cyclic Phenylglycinylphenylglycine in quantitative yield, which spontaneously self-assembled to give insoluble 2D mesosheets with large lateral dimensions.

Step II: Synthesis of (3S,6S)-3,6-diphenylpiperazine-2,5-dione

The dipeptide Fmoc-Phg-Phg-OMe (1 g, 1.82 moles) from the previous step, example 1, is subjected to Fmoc-deprotection in 15% piperidine/dichloro methane. The reaction mixture is evaporated to dryness and the residue is re-suspended in dichloromethane. The cyclic Phenylglycinylphenylglycine dipeptide spontaneously forms insoluble mesosheets. The suspension is filtered, washed with dichloromethane, methanol and dried to obtain cyclic Phenylglycinylphenylglycine (Phg-Phg) in quantitative yield. Relevant NMR data is provided herewith: 1H NMR (CDCI₃-CF₃COOH, 400 MHz) δ_Η 5.32-5.44 (d, 2H), 7.35- 7.55 (m, 10H), 8.22-8.38 (s, 2H,); ¹³C NMR (CDCI₃-CF₃COOH, 400 MHz) 5_C 59.1, 127.1, 129.6, 130.0, 133.9, 169.6; GCMS: 266.0 [M⁺] for C₁₆H₁₄N₂O₂, MW 266.2. Synthesis of cyclic Phenylglycinylphenylglycine [(3S,6S)-3,6-diphenylpiperazine-2,5- dione or cyclic (L-Phg-L-Phg)]

It is achieved through a robust and straight forward synthetic route developed as shown in Scheme 2. 9-Fluorenylmethyloxycarbonyl (Fmoc)- protected phenylglycine (Fmoc-Phg- OH) is condensed with phenylglycine methylester (H-Phg-OMe) using standard peptide coupling reagents to give the protected dipeptide Fmoc-Phg-Phg-OMe. The Fmoc-Phg- Phg-OMe is subjected to Fmoc-deprotection. During this deprotection process the dipeptide methylester undergo cyclization to give cyclic dipeptide in quantitative yield. Similarly other isomers are synthesized following the above described procedure.

Disclosed here is the simplest and cost effective synthetic procedure for the synthesis of cyclic dipeptide, as depicted in scheme 2. Since the cyclic dipeptide spontaneously self- assemble to give nano and meso sheets, simple filtration is enough to obtain the cyclic dipeptide.

Example: 4 FESEM and HRTEM of cyclic Phenylalanylphenylalanine [(3S,6S)-3,6- dibenzylpiperazine-2,5-dione (CDP 1) or cyclic (Phe-Phe)]

Field emission scanning electron microscopy (FESEM): SEM measurements are performed using an FESEM, FEI QUANTA 3D FEG 600 microscope or FESEM, FEI Nova-Nano SEM-600 equipped with a gun and field emission gun operating at 30 kV. High resolution transmission electron microscopy (HRTEM): Samples are prepared by placing a 10 μΐ aliquot of the cyclic dipeptide suspension or solution on a 200 mesh holey carbon supported copper grids. After removing excess fluid, sample is dried at room temperature to remove the solvent. HRTEM images are obtained from JEOL JEM 3010 electron microscope operating at 300 kV.

The c c/zc-(Phe-Phe) nanofibers and fiber bundles are characterized by field emission scanning electron microscope (FESEM) and high resolution transmission electron microscope (HRTEM). Figure 2 show the FESEM and HR-TEM images of CDP 1 suspended in dichloromethane. Formation self-assembled nanofibers, nanofiber bundle and fiber bundles of thickness of < 200 nm (seen in Figure 2b), ~700-900 nm and 1-2 μηι respectively are observed. FESEM images also reveal the coexistence of nanometer to micrometer thick fiber-bundles (Figure 2a-b). The cyclic dipeptide fiber bundles are of several millimeters long such that they are visible to naked eye upon careful observation. The solid nature of the fiber bundle is confirmed by ion beam milling of an isolated bundle under scanning electron microscope (Figure 2d). The ion beam is directed to cut the bundle at predetermined point. The cross section of ends resulted from the ion beam milling of fiber bundle confirms its fiber nature. Data from FESEM are further substantiated by HRTEM images (Figure 2B). The TEM data reaffirms the coexistence of nano and micrometer thick fiber bundles. This coexistence of nano and micrometer thick fiber bundles implies that nanofiber undergo further self-assembly to form nano and micrometer thick fiber bundles. CDP 2 [Unnatural D-Isomer] is also found to form fiber bundles similar to CDP 1 [Natural L-Isomer] . Though the fibers reported here are bundles of nanofibers, for the sake of better clarity of understanding the terminology of nanofibers (< 200 nm thick), fibers (< 900 nm thick) and fiber bundle (> 1 μηι thick) are used. The hierarchy in fibers observed with CDP 1 is very much similar to fibrils, fibers, and fiber bundles that observed in collagen and spider silk.

Example: 5 Solubility of cyclic Phenylalanylphenylalanine [(3S,6S)-3,6- dibenzylpiperazine-2,5-dione (CDP 1) or cyclic (Phe-Phe)] To further understand the molecular mechanism and structural topography underlying the self-assembly of CDP l(35',65)-3,6-dibenzylpiperazine-2,5-dione) to form fiber bundles it is sought to find a suitable solvent which can dissolve fiber bundles into solution. Attempt to solublize CDP 1 fibers revealed that organic solvents such as dichloromethane, chloroform dissolve the fiber bundles into clear solution upon acidification. The fiber bundles are also found to dissolve in fluorinated solvents in general and 1 , 1 , 1, 3, 3, 3-hexafiuoro-2-propanaol (HFP) in particular. However fiber bundles are insoluble in methanol and water even after acidification. Only organic acids such as acetic acid and trifiuoroacetic acid (TFA) are used to solublize cyclic dipeptide fiber bundles into organic solvents such as dichloromethane and chloroform and aqueous mineral acids are avoided as they may induce fiber precipitation. These solubility experiments revealed in depth knowledge about the formation nanofibers and fiber bundles with nanometer to micrometer thickness. First CDP 1 fiber bundles are suspended in methanol and acidified with acetic acid, the fibers remained as insoluble suspension. The sample is analyzed using FESEM and HRTEM (Figure 3A&B). These data show that the integrity of the fiber bundles retained except for length of the fibers. High resolution image (Figure 3B) show that nanofibers project out at the ends of a fiber bundle. It appears that the fiber bundles shortened to some extent due to the presence of acid, however the fibers are still appreciably long and the bundle size remained intact. TEM data (Figure 3) revealed with highest clarity that the nanofibers self-assembled to form bundles as it can be seen from the ends where nanofibers projecting out from the fiber bundles. Next solutions of CDP 1 are prepared in dichloromethane-acetic acid (6 μΙ mL) and HFP. The self-assembly of CDP 1 from its freshly prepared solutions is studied by FESEM and HRTEM. Fiber bundles formed spontaneously as the solvents evaporated on the surfaces. In case of dichloromethane-acetic acid as a solvent, nanofibers and fibers which make the fiber bundles are seen projecting out at the ends of the fibers (Figure 4A). Figure 4A provides FESEM images of CDP 1 formed from the solutions of CDP 1 in dichloromethane with acetic acid, the accompanied high resolution image (right) of the selected region show micrometer size fibers are a self assembled collection of nanofibers and nanofiber bundle. Inset on the right image further highlight the fiber bundle topography. Figure 4B provides FESEM images of CDPl formed from the solutions of CDP 1 in l ,l,l ,3,3,3-Hexafluoro-2-propanaol. The accompanied image is of high resolution images of the selected region that show fibers are indeed a bundle of collection of nanofibers. The pointers show hierarchy exists in the nanofiber collection found in micrometer thick fiber bundle.

Fiber bundles formed from the solution of CDP 1 in HFP provided much more insight into the hierarchy involved in the self-assembly of CDP 1 (nanofibers, fibers and fiber bundles) similar to that of collagen fibrils, fibers and fiber bundles. Though the fiber bundles formed instantaneously from the solution of CDP 1 in HFP, fiber bundles with loosely assembled but still intact nanofibers and fibers were observed (Figure 4B) and there also exists some compact fiber bundles. This observation is probably attributed to the solvent interaction with CDP 1 molecules and to some extent the difference in their boiling points of two solvents used, dichloromethane (40 °C) and HFP (58.2 °C). Fibers formed from HFP solution loses solvent slowly due to the strong interaction of HFP with CDP 1 and relatively low volatility compare to dichloromethane and hence the residual solvent prevents spontaneous self-assembly of fibers to form compact fiber bundles. Nevertheless these loosely assembled fiber bundles provided much needed insight into the understanding of their structural topography and assembly formation beyond doubt. The self-assembly of CDP 1 nanofibers to fibers and then to fiber bundles is further confirmed from the HRTEM images of fiber bundles formed from the solution of CDP 1 in HFP (Figure 5 A &B). These images not only confirmed that the micrometer fibers are indeed bundles of nanofibers but also the coexistence of fibers and fiber bundles.

Example 6: Gelation experiments on cyclic Phenylalanylphenylalanine [(3S,6S)-3,6- dibenzylpiperazine-2,5-dione (CDP 1) or cyclic (Phe-Phe)]

For the application view point it is necessary to understand the gelation property of cyclic dipeptide in organic solvent which come handy in processing of cyclic dipeptide fiber bundles depending on the nature of application. As described in the previous section, CDP l [(35',65 -3,6-dibenzylpiperazine-2,5-dione] is found to dissolve in organic solvents such as dichloromethane and chloroform upon acidification.

Next the gelation property of CDP 1 in chloroform against the concentration of TFA is undertaken. Specifically TFA is used because of the absence of methyl protons that is useful in comparative analysis of the data from other techniques. As shown in Figure 6 A, an equal amount of CDP 1 (2.5 mg/ml) is suspended in chloroform in vials 1-4 at 25°C. To determine the amount of TFA required to dissolve the suspended fiber bundles in to chloroform solution, TFA is added to vials 1-4 in the order of increasing concentrations, 3.0 μΐ,, 6.0 μΐ, 12.0 μΐ, and 24 μΐ respectively. The samples are stored overnight at room temperature. CDP 1 in vial 4 dissolves immediately after the addition of TFA to give clear solution and vials 1-3 remained suspensions. Vials 1-4 are allowed to stand overnight at room temperature. The CDP 1 in vial 3 (12 μΐ of added TFA) results in the formation fibrous gel, as confirmed by no free flow of suspension even after inverting the vials and vials 1 and 2 remained suspensions [Figure 6A(b)]. This indicates the critical concentration of TFA required for converting CDP 1 suspension in chloroform to gel, above which CDP 1 dissolves to give clear solution and below the critical concentration of TFA CDP 1 in chloroform exists as suspension. Fibrous gel is an intermediate state of CDP 1 between insoluble fiber bundles suspension and clear solution in chloroform upon addition of TFA. Now it is possible to have CDP 1 as a 1) insoluble fiber bundle suspension, 2) fibrous gel and 3) clear solution with added acidifying agent. In general the option of having CDP 1 in different forms is very useful in processing fiber bundles into many different shapes and sizes depending on the nature of application. To understand the changes that occur to the material nature and structural topography of fiber bundles of CDP 1 in chloroform with varying concentrations of added TFA, FESEM images are taken for the samples from vials 1-4 as shown in Figure 6B. Interestingly these images provided clear idea about the changes occurred to the structure of fiber bundles, from CDP 1 suspension to clear solution in chloroform through the state of fibrous gel. The fiber bundles starts to organize into a dense compact form with added TFA but still in suspended form in vials 1 and 2. At critical concentration of TFA i.e. in vial 3 the fibrous gel found to contain nanofiber bundles assembled in a very compressed state. The clear solution of CDP 1 (vial 4) formed fiber bundles short length. These topographical changes to fibrous material are further confirmed from Infrared spectroscopic analysis.

FT-IR spectra of CDP 1 suspension, gel and solution in chloroform are recorded on sodium chloride and KBr pellets on a Bruker IFS 66v/S FT-IR spectrometer. In FT-IR spectra of the above samples (vial 1 -4) along with CDP 1 in dry form and suspension in chloroform have shown the topographical changes occurred to fibers during the transition of Cyclic Dipeptide suspension in chloroform to a fibrous gel state as in vial 3 (Supporting Information). The changes are observed in the region ~3300-2500 cm^"1, broadening and shift of peaks between ~1680-1535 (by 12 and 28 cm^"1), at 1457 and 1460 cm^"1. Appearance of new peaks at 1212 and 1 180 cm^"1 is also observed. All these changes are attribute to NH, amide I, amide II, aromatic C=C and =C-H as result of the variation in the hydrogen bonding and π- π interactions.

Example 7: Thermogravimetric analysis (TGA) of cyclic Phenylalanylphenylalanine [(3S,6S)-3,6-dibenzylpiperazine-2,5-dione (CDP 1) or cyclic (Phe-Phe)]

In continuation to Figure 6 of Example 6, the fiber bundle stability data is provided. Thermogravimetric analysis (TGA) is used to investigate the structural changes and stability in particular of the samples from vial 1-4 (as mentioned in example 6) along with CDP 1 fiber bundles in solid form and suspended in chloroform (Figure 7). The CDP 1 solid fiber bundles, suspension in chloroform and fibrous gel samples shows multiple transitions which attribute to the bundle nature of the fibers. All the samples thermally decompose in the temperature range of ~245-400°C. The CDP 1 fiber bundle (solid form) shows two major transitions at 324.9 and 390.8°C. The thermal decomposition temperature at 390.8°C clearly indicates the high stability of the fiber bundles. The TFA treated CDP 1 suspension in vial 1 and 2 exhibits relative decrease in thermal stability. However the fibrous gel sample from vial 3 exhibited high thermal stability (342.4°C) compared to the samples from vials 1 and 2 but slightly less than CDP 1 solid sample. The relative high stability of fibrous gel sample is accompanied by multiple transition temperatures (major transitions: 227.4, 297.6, and 342.4°C). The solution sample from vial 4 did not show clear transition compare to other samples. These studies indicate that there is a clear change in the structure and topography of the fiber bundles. Remarkably high stability observed with CDP 1 fiber bundles in the solid form and fibrous gel is very useful property that is exploited for processing Cyclic Dipeptide fiber bundles for various applications.

Thermogravimetric analysis (TGA) is carried out on Mettler Toledo, TG-850 instrument under flowing nitrogen atmosphere (40 mL min ¹) at a heating rate of 10°C min^-1, with total temperature range of 30-700°C. The CDP 1 suspended and solution samples are dried at room temperature before subjecting to TGA analysis. The TGA Analysis data is presented in figure 7.

Example 8: FESEM and HRTEM Studies of cyclic phenylglycinylphenylglycine [(3S,65)-3,6-diphenylpiperazine-2,5-dione or cyclic (L-Phg-L-Phg)]

In FESEM micrographs 2D mesosheets which also includes rhomboid shape and > 10 μηι lateral dimensions are observed (Figure 8 a). This is further substantiated by HRTEM micrograph (Figure 8b), which revealed the existence of a layered hierarchy (Figure 8b, inset) similar to the structure of graphene.

In an embodiment of the present disclosure, attempts to solubilize the spontaneously self- assembled cyclic Phenylglycinylphenylglycine (Phg-Phg) mesosheets in organic solvents provided valuable insights. Cyclic Phenylglycinylphenylglycine (Phg-Phg) is found to dissolve in CHCI₃ and CH₂CI₂ upon acidification with trifluoroacetic acid (TFA). The solution of Cyclic dipeptide Phenylglycinylphenylglycine (Phg-Phg) in CHCI₃-TFA upon solvent evaporation formed well separated 2D nanosheets (Figure 8c and 8d). Nanosheets are also obtained from the solution of 1 in CH₂CI₂-TFA. This represents an indirect and alternative method for the exfoliation of nanosheets from 2D mesosheets. The 2D mesosheets possessed high thermal stability as determined from thermogravimetric analysis (Figure 9). The cyclic Phenylglycinylphenylglycine (Phg-Phg) mesosheets (solid sample) showed two transitions which are attributed to hierarchical organization of the 2D sheets. Major transitions are observed at 220.9 and 310.1 °C. A thermal decomposition temperature of 310.1 °C clearly indicates high stability. This provides supporting evidence for the existence of morphological hierarchy involving the self- organized nanosheets to form stable mesosheets.

In an embodiment of the present disclosure, AFM studies on cyclic Phenylglycinylphenylglycine (Phg-Phg) suspended in methanol revealed the presence of 2D mesosheets with smooth and large topographical lateral surface as shown in Figure 10. The height profile (Figure 10c) indicates a thickness -300 nm with a well defined shape. On the other hand, the AFM height profile of 2D nanosheets (formed by the solution of 1 in CHCI₃-TFA) indicate a layer thickness of ~60 nm, suggesting that the nanosheets initially form by self-assembly which then self-organize to produce 2D mesosheets with large lateral surface area and sub-micrometer multi-layer thickness. In an embodiment of the present disclosure, solution of cyclic-Phg-Phg (Phenylglycinylphenylglycine) in l,l ,l,3,3,3-hexafluoro-2-propanol (HFP) is used to gain further insight into the morphological changes in the formation of 2D sheets. Figure 11a show star-shaped structures with micrometer dimensions. These structures resemble the star/flower shaped patterns formed by molecules of organic and inorganic nature. These meso-structures consist of self-organized nanosheets in two dimensions (Figure 1 lb). HRTEM images of Phenylglycinylphenylglycine in HFP confirmed the formation of star-shaped patterns (Figure 1 1c and l id). The formation of these presumably occurs through the diffusion- limited aggregation. Figure l id show the HRTEM image of star branch edge revealing the presence of nanosheets. The structural topography of star- shaped patterns is studied by atomic force microscopy (Figure l ie). The AFM image at the star branch edge revealed that these patterns consist of self-organized nanosheets and the corresponding height profile has showed the topographical thickness of constituent nanosheets is of ~30 nm (Figure 1 If). The AFM height profile (Figure 1 If) also reveals that constituent nanosheets relatively are of uniform thickness (a = b ~ 30 nm). The figure 12 depicts the FESEM micrographs of 2D mesosheets (which also includes rhomboid shape) of cyclic (Phg-Phg) Phenylglycinylphenylglycine. The figure 13 shows the HRTEM micrographs of cyclic Phenylglycinylphenylglycine (Phg-Phg) mesosheets and the figure 14 shows FESEM micrographs of 2D nanosheets formed from the solutions of cyclic Phenylglycinylphenylglycine (Phg-Phg). The figure 15 shows AFM image of 2D nanosheets formed from the solution of cyclic Phenylglycinylphenylglycine (Phg-Phg). Further, analysis of (Z⁾-Phg-Z-Phg), one of the isomers in cyclic (Phg-Phg) series is done. The FESEM analysis of 2D rhomboid sheets of cyclic (Z⁾-Phg-Z-Phg) in methanol is depicted in figure 16(a) as a FESEM micrograph. Figure 16(b) shows the HRTEM micrograph of cyclic (Z⁾-Phg-Z-Phg) suspended in methanol. Figure 16(c) to 16(f) depicts the AFM image of rhomboid 2D sheets, high resolution image of the 2D sheet edge showing the existence layered hierarchy, FESEM micrograph of flowers formed by the solution of cyclic (Z⁾-Phg-Z-Phg) in chloroform-TFA and high resolution images of nanosheets formed by the solution of cyclic (Z⁾-Phg-Z-Phg) in chloroform-TFA. These nanosheets form aggregates (flowers) as result of diffusion-limited solvent evaporation. Example 9a: NMR Spectroscopy, Solution State NMR experiments of cyclic phenylglycinylphenylglycine [(3S,65)-3,6-diphenylpiperazine-2,5-dione or cyclic (L- Phg-L-Phg)]

NMR experiments are performed at 25 °C on a Bruker Avance 500 MHz spectrometer equipped with Z-axis gradient. About 5 mg sample cyclic Phenylglycinylphenylglycine [(35',65)-3,6-diphenylpiperazine-2,5-dione] consisting of the mesosheets is added to 500 ul CDCI₃ and transferred to a 5 mm NMR tube. The ID ^!H experiments are acquired with a relaxation delay between scans of 4 s with H carrier frequency set at 4.7 ppm. A H pulse length of 7.75 us is used. 8192 points are collected with a spectral width of 14 ppm with 8 scans per FID. The formation of monomeric peptide units is monitored by titrating a suspension of mesosheets of cyclic Phenylglycinylphenylglycine in CDCI₃ with trifluoroacetic acid (TFA) until complete dissolution is obtained. Upon each addition (1 UL) of TFA, ID 1H and 2D [¹⁵N, 1H] HSQC¹ spectra are acquired. The 2D [¹⁵N, 1H] HSQC is acquired with a relaxation delay between scans of 1 s with 1H and ¹⁵N carrier positions set to 4.7 and 117 ppm, respectively. A 90° pulse length of 8.5 US and 39 US are used for ^!H and ¹⁵N, respectively. Signal averaging is achieved with 16 scans acquired per FID resulting in a measurement time of 1 hour 40 minutes for each 2D experiment. The amide temperature coefficients upon each addition of TFA are obtained by measuring the changes in the amide proton chemical shift in the ID ^!H spectrum at three different temperatures: 289 K, 298 K and 308 K. Two dimensional ['Η- 'Η] ROESY spectra is acquired with 2048 and 256 points, respectively, in coi and ω₂ with a spectral width of 12 ppm in both the dimensions. Signal averaging is achieved with 32 scans acquired per FID (Total Measurement time: 4 hours 30 minutes). Example 9b: Solid State NMR experiments of cyclic phenylglycinylphenylglycine [(3S,65)-3,6-diphenylpiperazine-2,5-dione or cyclic (L-Phg-L-Phg)]

NMR experiments are performed at 25 °C on a Bruker Avance III 500 MHz spectrometer equipped with 2.5 mm Magic Angle Spinning (MAS) probe. Approximately, 15 mg of a powder sample cyclic Phenylglycinylphenylglycine [(35',65 -3,6-diphenylpiperazine-2,5- dione] containing the mesosheets is filled in a 2.5 mm rotor. The MAS rate is constantly maintained at 1 1,1 11 ± 3 Hz with ^!H and ¹³C 90° pulse widths of 4us. A relaxation delay between scans of 5s is used in all the experiments with the ¹³C and ^!H carrier positions set at 114 ppm and 6 ppm, respectively. In an embodiment of the present disclosure, the ID 1 H - 13 C Cross Polarization (CP) experiment is performed using a contact time of 2 ms with a radio-frequency (RF) field strength of 62.5 kHz for ^!H and 51.4 kHz for ¹³C. Heteronuclear (^!H-¹³C) decoupling is achieved during acquisition using the TPPM-15 scheme with a RF field strength 83.3 kHz. 1024 points are collected for a spectral width of 301 ppm resulting in an acquisition time (i_max) of 13.5ms with 8192 scans for signal averaging (total measurement time ~12 hours).

In an embodiment of the present disclosure, the 2D ^!H-¹³C 2D HETCOR experiment is performed by applying a LG decoupling scheme in the indirect (ti) ^!H dimension using a LG pulse length of 13.7 us. Subsequent magnetization transfer from ^!H to ¹³C is obtained using a CP with contact time of 3.5 ms. Spectral widths of 301 ppm for ¹³C and 14 ppm for H are used and 752 and 36 data points are collected resulting in an acquisition time (/max) of 10 ms and 5.1 ms, respectively, in the two dimensions. Heteronuclear (^!H-¹³C) decoupling is achieved during acquisition using the TPPM-15 scheme as described for the ID CP experiment above. The signal is averaged over 256 scans (Total measurement time 10 hours).

In an embodiment of the present disclosure, solution and solid-state NMR spectroscopy is used to understand the different interactions involved at a molecular level (The details of the experimental set-up and the acquisition parameters used are provided above in the general experimental procedure section). First, the formation of monomeric peptide units is monitored by titrating a suspension of mesosheets of cyclic Phenylglycinylphenylglycine [(35',65)-3,6-diphenylpiperazine-2,5-dione] in CDC1₃ with trifluoroacetic acid (TFA) until complete dissolution was obtained. Upon each addition (1 HL) of TFA (marked i-v in Figure 17a), ID 1H and 2D [¹⁵N, 1H] HSQC spectra are acquired. In the mesosheets, the amide proton ('Η¹^) and ¹⁵N have upfield shifts of 6.2 ppm and 115 ppm, respectively. Such upfield shifts result from the ring-current effect in mesosheets as the amide protons are located in shielding zone of closely stacked aromatic rings. These resonances exhibit a shift to downfield regions of the spectrum upon addition of TFA (Figure 17b), which is attributed to disruption of intermolecular hydrogen bonds caused by the dissociation of sheets into monomeric units. This is further verified by acquiring ID 1H spectra for each addition of TFA at three different temperatures. The amide proton temperature coefficients are observed to be -3 ± 0.1 ppb/K in mesosheets indicating strong hydrogen bonds and -12 to -14 ppb/K upon dissolution in TFA. Thus, hydrogen bond interactions present in the mesosheets are disrupted by addition of TFA. Notably, on dissolution in CDCI₃-TFA, the amide proton showed cross peaks arising from chemical exchange with the carboxylic proton of TFA in the 2D ROESY spectrum. Further, the cis-conformation of the two phenyl rings in cyclic Phenylglycinylphenylglycine (Z-Phg-Z-Phg) is validated by the absence of a doublet for the 1H^a signal (Figure 17) due to 3- bond scalar coupling to 1H^N (³J(H^N-H^a)), implying that the J is smaller than the line width (~4 Hz). This is due to the fact that the cis-conformation results in the backbone torsion angle, Φ , to be almost 90°. The ID ^!H- ¹³C CP and 2D ^!H-¹³C HETCOR experiments carried out in the solid-state under MAS (Figure 17c and 17d) provided ¹³C chemical shifts in the 2D mesosheet form, which could not be obtained in solution due to low sensitivity. The ¹³C^a and ¹³CO chemical shift of -60 ppm and -169 ppm, respectively correspond to that observed in cis-amides of cyclic dipeptides. Evidently the shifts of 5.3 ppm, 6.2 ppm and 7.4-7.5 ppm for 'Η", ^{i N} and aromatic ¾ respectively, obtained from 2D HETCOR match closely the shifts observed in solution (Figure 17), thereby validating the solution state SMR data.

The formation of nanosheets by solution of cyclic Phenylglycinylphenylglycine in acidified organic solvent (CHCI₃-TFA and CH₂CI₂-TFA) is an indication that mesosheets consist of layered assembly of nanosheets. This layered hierarchy is identical to that observed in graphene. Further, in a fluorinated solvent, cyclic Phenylglycinylphenylglycine forms star-shaped patterns by self-organization of nanosheets through diffusion-limited aggregation. Such star-shaped patterns could also be an intermediate state through which initially formed nanosheets undergo further self- organization to form 2D mesosheets (Figure 18). NMR studies reveal that 2D sheets consist of a strong network of hydrogen bonded layers of cyclic Phenylglycinylphenylglycine along with aromatic π-π stacking. The plot of amide temperature coefficient at different additions of TFA is captured as figure 19 and figure 20 depicts the plot of a region of 2D 1H] ROESY spectrum.

Example 10: Thermogravimetric analysis (TGA) data for cyclic phenylglycinylphenylglycine [(3S,65)-3,6-diphenylpiperazine-2,5-dione or cyclic (L- Phg-L-Phg)]

Thermogravimetric analysis (TGA) is carried out on a Mettler Toledo TG-850 instrument under flowing nitrogen atmosphere (40 mL min ¹) at a heating rate of 10°C min^-1, with total temperature range of 30-600°C.

• cyclic (Z-Phg-Z-Phg) 2D mesosheets.

In an embodiment of the present disclosure, thermogravimetric Studies are conducted on the 2D mesosheets of cyclic (Z-Phg-Z-Phg) and they are found to be stable up to a temperature of 325°C. The figure 9 shows thermogravimetric analysis (TGA) of cyclic Phenylglycinylphenylglycine 2D mesosheets (solid). The weight losses are determined by first derivative (DTG, red) curve. Main transitions observed are 220.9 and 310.1°C, an indication of existence of self-organized structural hierarchy (nanosheets and mesosheets).

• Cyclic D-Phg-Z-Phg) 2D mesosheets.

In an embodiment of the present disclosure, thermogravimetric Studies are conducted on the 2D mesosheets cyclic (Z⁾-Phg-Z-Phg). The figure 21 shows the Thermogravimetric analysis (TGA) of cyclic D-Phg-Z-Phg) 2D mesosheets (solid). The weight losses are determined by first derivative (DTG, red) curve. Main transitions observed are 306.9 and 497.3°C, an indication of existence of self-organized structural hierarchy (nanosheets and mesosheets). The 2D mesosheets are found to be stable up to 500°C. Example 11: Crystallization studies

The following data reveals that crystalline patterns are formed on insoluble 2D sheets of cyclic D-Phg-Z-Phg) in methanol over a period of two months. Suspended 2D mesosheets in methanol act as self-templates for crystalization where cyclic (Z⁾-Phg-Z- Phg) molecules start crystallizing on surface to form well-defined patterns. This technique is highly useful in fabricating template-assisted crystalline patterns.

In an embodiment of the present disclosure, figure 22, shows the transformation of self- assembled 2D mesosheets of cyclic (Z⁾-Phg-Z-Phg) into crystals in methanol after 2 months. Specifically, the figure 22(a) to 22(d) provides FESEM, HRTEM and AFM images showing the formation of cyclic (Z⁾-Phg-Z-Phg) crystallites on the surface of self- assembly based 2D mesosheets. The crystallization occurs in a precise pattern. AFM height profile shows the thinning of 2D mesosheets as the crystallization process is initiated on its surface (2D sheet thickness -120 nm, thickness of crystallites ~ 64 nm). In an embodiment of the present disclosure, further, Rhomboid single-crystalline 2D sheets of cyclic (Z⁾-Phg-Z-Phg) are formed in 2-methoxyethanol. The shape of these crystals is similar to that of rhomboid 2D mesosheets formed by self-assembly based aggregation. This aspect is depicted in figure 23 wherein the Optical profiler image and analysis is provided. The size of the rhomboid crystalline sheets is relatively larger compared to 2D mesosheets (lateral dimension > 600 μηι). The height of crystalline sheet is found to be ~ 300 μηι. Scale bar: 350 μηι (d) crystal packing of cyclic D-Phg-Z-Phg) into molecular-layers.

In an embodiment of the present disclosure, smallest of the cyclic peptides has been developed to form fiber bundles which mimics in a way similar to nature does in the production of fiber bundles of biological origin such as spider silk, collagen etc. Novel and clean synthetic route is developed to access cyclic dipeptide without involving cumbersome purification procedures that are common in organic synthesis. It has been shown that cyclic dipeptide (c c/z^'c-Phe-Phe) can form fibers and fiber bundles with thickness ranging from nano- to micro-meters and of millimeter length, similar to the production of biological fibers from large peptide and proteins in living systems. Cyclic- Phe-Phe is shown to form insoluble fiber suspension, fibrous gel and clear solution in organic solvents; this is very useful to process Cyclic Dipeptide fibers and fiber bundles for various application types. Large scale production of Cyclic Dipeptide fiber bundles scores over the biotechnology based production of biological fibers which are practically inefficient. Cyclic Dipeptide fibers and fiber bundles has high impact in biomaterials applications such as cell cultures, tissue engineering, regenerative and biomedical research such as suture, neurological regeneration, organ replacement etc and in general any applications that require fibrous materials. Since the simplicity, versatility and cost effectiveness involved in the large scale production of macroscopic Cyclic Dipeptide fiber bundles with nanoscale order is an added advantage and hence their potential applications such as in fabrication of bandages, medical fabrics and degradable medical materials may become a reality. This also paves the way for developing new modular and synthetic small organic molecules that undergo supramolecular self-assembly (similar to the concept of supramolecular polymers) to form fibers, fiber bundles and many other biomaterials mimicking materials of bio-origin which are need of the moment. In an embodiment of the present disclosure, the formation of cyclic Phenylglycinylphenylglycine based 2D sheets and their topographical hierarchy, high thermal stability, and in particular strong hydrogen bonds along with aromatic π-π interactions opens up new avenues for the design of novel biomaterials. For instance, 2D nano and mesosheets of cyclic Phenylglycinylphenylglycine can be viewed as potential candidates in applications such as biominerahzation, cell culture, tissue engineering, stem cell growth, drug delivery and 2D sheets derived composites as optoelectronic materials.

In an embodiment of the present disclosure, the cyclic dipeptides of the instant disclosure showed various applications. The higher structure fiber bundles of cyclic Phe-Phe are electrospinned into threads, fabrics, suture, bandage materials can be produced. They are also useful in cell culturing, tissue culturing, drug delivery system, as composite materials, as inhibitors of fibrillization (useful in the neurodegenerative diseases such as Alzheimer's and Parkinson's disease) and in Biomedical research such as neurological regeneration and organ replacement studies.

In an embodiment of the present disclosure, for instance, fiber bundles of cyclic (Phe- Phe) could be potential candidates for biomaterial applications, such as:

a) Production of suture (for stitching wounds),

b) Production of fabrics (spinning of fibers into fabrics which are used as medical fabrics, bandages etc),

c) In cell culture/tissue culture: cyclic (Phe-Phe) fiber bundles can be used as templates in the neuorological reproduction,

d) As drug envelopes which find application in drug delivery,

e) Composites of cyclic (Phe-Phe) fiber bundles with natural materials such as collagen, hydroxyapatite and unnatural materials such as various nanoparticles, would give rise to hybrid materials with range of biomaterial applications (eg. Replacement of bone, cartilage and also as artificial skin),

f) Their aromatic structures, highly ordered structures and doped materials find applications as optoelectronic or dielectric materials, g) Since the peptide sequence (Phe-Phe) is homologous to beta-amyloid peptide, cyclic (Phe-Phe) can be used as an inhibitor for the beta-amyloid aggregation in diseases such as Alzheimer's.

The cyclic dipeptide- cyclic (Phg-Phg), based Nano and Mesosheets find applications in Biomineralization, as Biomaterials, in drug delivery, as 2D sheets derived composites for optoelectronic materials and as Inhibitors of fibrillization in neurodegenerative diseases such as Alzheimer's and Parkinson's.

For instance, nano- and mesosheets of cyclic (Phg-Phg) are useful in biomaterial applications, such as:

a) Cyclic (Phg-Phg) sheets are used as templates in cell culture and tissue culture, particularly for stem cell growth. These sheets in their original form or modified form act as templates for differentiation of stem cells into different tissue cells. b) Cyclic (Phg-Phg) based materials are used as drug envelopes which find application in drug delivery system.

c) Composites of cyclic (Phg-Phg) nano- and mesosheets with natural materials such as collagen, hydroxyapatite and unnatural materials such as various nanoparticles would give rise to hybrid materials have a range of biomaterial applications (eg. Replacement of bone, cartilage and as artificial skin).

d) Their aromatic structures, highly ordered structures and doped materials find applications as optoelectronic or dielectric materials. The sheet scaffolds (shape of nano- and mesosheets) are particularly interesting and are desired in many of the optoelectronic/dielectronic applications.

e) Since the peptide sequence (Phg-Phg) is mimic of homologous (Phe-Phe) sequence in beta-amyloid peptide, cyclic (Phg-Phg) can be used as inhibitor for the beta-amyloid aggregation in diseases like Alzheimer's.

Claims

We claim:

1) A synthetic cyclic dipeptide which self assembles to form nano, meso and micro structures.

2) The cyclic dipeptide as claimed in claim 1, wherein the dipeptide is obtained from amino acids with stereochemistry selected from a group comprising (R,R), (S,S),

(R,S) and (S,R).

3) The cyclic dipeptide as claimed in claim 1, wherein the dipeptide is obtained from amino acids selected from a group comprising natural aromatic amino acids, unnatural aromatic amino acids, derivatives of amino acids and any combination thereof.

4) The cyclic dipeptide as claimed in claim 1 , wherein the amino acids are selected from a group comprising Phenylalanine, Phenylglycine and combination thereof.

5) The cyclic dipeptide as claimed in claim 1, wherein the dipeptide is 3,6- dibenzylpiperazine.

6) The cyclic dipeptide as claimed in claim 1, wherein the dipeptide is 3,6- dibenzylpiperazine-2-5-dione.

7) The cyclic dipeptide as claimed in claim 1, wherein the dipeptide is 3,6- diphenylpiperazine.

8) The cyclic dipeptide as claimed in claim 1, wherein the dipeptide is 3,6- diphenylpiperazine-2,5-dione.

9) A self assembled nano, meso and micro structure of synthetic cyclic dipeptide of claim 1.

10) The self assembled structure as claimed in claim 9, wherein the dipeptide is 3,6- dibenzylpiperazine.

11) The self assembled structure as claimed in claim 9, wherein the dipeptide is 3,6- dibenzylpiperazine-2-5-dione.

12) The self assembled structure as claimed in claim 9, wherein the dipeptide is 3,6- diphenylpiperazine.

13) The self assembled structure as claimed in claim 9, wherein the dipeptide is 3,6- diphenylpiperazine-2,5-dione. 14) The self assembled structure as claimed in claim 9, wherein the nano, meso and micro structure is selected from a group comprising nanofibers, nanofiber bundles, fibers, fiber bundles, nanotubes, nanotube bundles, nanosheets, mesosheets, 2D sheets and gels.

15) The self assembled structure as claimed in claim 14, wherein the meso and 2D sheets have layered hierarchy.

16) A process for preparation of cyclic dipeptide, the process comprising steps of:

b) deprotecting the protected dipeptide to obtain the cyclic dipeptide.

17) A process for preparation of nano, meso and micro structures of cyclic dipeptide, the process comprising steps of:

18) The process as claimed in claims 16 and 17, wherein the preparation is carried out at a temperature ranging from about 0°C to about 50°C, preferably about 25°C.

19) The process as claimed in claims 16 and 17, wherein the ester is amino acid ester. 20) The process as claimed in claim 16 and 17, wherein the amino acid is selected from a group comprising natural aromatic amino acid, unnatural aromatic amino acid, derivates of amino acids and any combination thereof, with stereochemistry selected from a group comprising (R,R), (S,S), (R,S) and (S,R).

21) The process as claimed in claims 16 and 17, wherein the condensing reaction is carried out for a time period ranging from about 1 h to about 12 h, preferably about 5 h.

22) The process as claimed in claims 16 and 17, wherein the coupling reagent is selected from a group comprising l-Ethyl-3-(3-dimethylaminopropyl) carbodiimide, 1- hydroxybenzotriazole, Diisopropylehtylamine, 0-(lH-benzotriazole-l-yl)-N,N,N',N'- tetramethyluronium hexafluorophosphate, 0-(lH-benzotriazole-l-yl)-N,N,N',N'- tetramethyluronium tetrafluoroborate, Dicyclohexylcarbodiimide, diisopropylcarbodiimide, (Benzotriazol- 1 -yloxy)tris(dimethylamino)phosphonium hexafluorophosphate, 0-(7-Azabenzotriazol- 1 -yl)-N,N,N' ,N'-tetramethyluronium hexafluorophosphate , 0-(6-Chlorobenzotriazol-l-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, 0-(3,4-Dihydro-4-oxo-l,2,3-benzotriazine-3-yl)-N,N,N',N'- tetramethyluronium tetrafluoroborate, benzotriazol- 1-yl- oxytripyrrolidinophosphonium hexafluorophosphate and Carbonyldiimidazole.

23) The process as claimed in claims 16 and 17, wherein the deprotection is achieved using a base at a concentration ranging from about 1 % to about 100 %, preferably about 10 % in a solvent for a time period ranging from about 0.5 h to about 24 h, preferably for about 2 h.

24) The process as claimed in claim 23, wherein the base is selected from a group comprising piperidine, ammonia, morpholine, sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, sodium hydride, n-butyl lithium, sodium amide, piperidine, ammonia and morpholine.

25) The process as claimed in claim 23, wherein the solvent is an organic solvent selected from a group comprising dichloromethane, dimethylformamide, acetonitrile and toluene.

26) The process as claimed in claims 16 and 17, wherein the dipeptide is 3,6- dibenzylpiperazine.

27) The process as claimed in claims 16 and 17, wherein the dipeptide is 3,6- dibenzylpiperazine-2-5-dione.

28) The process as claimed in claims 16 and 17, wherein the dipeptide is 3,6- diphenylpiperazine.

29) The process as claimed in claims 16 and 17, wherein the dipeptide is 3,6- diphenylpiperazine-2,5-dione.

30) The process as claimed in claim 17, wherein the nano, meso and micro structure is selected from a group comprising nano fibers, nano fiber bundles, fibers, fiber bundles, nanotubes, nanotube bundles, nanosheets, mesosheets, 2D sheets and gels.

31) The process as claimed in claim 17, wherein the meso and micro structure are formed by self assembly of nano structures. 32) The process as claimed in claim 17, wherein the nano, meso and microstructures are crystalline or non-crystalline in nature.

33) The process as claimed in claim 17, wherein the meso and micro structure are soluble in solvents selected from a group comprising acidified organic solvents and fluorinated solvents.

34) The process as claimed in claim 33, wherein the organic solvents are selected from a group comprising dichloromethane, chloroform, ethylacetate, cyclohexane, hexane, toluene, dimethylformamide and dimethylsulfoxide; and the fluorinated solvents are selected from a group comprising hexafluoroisopropanol and tetrafluorethanol.

35) The process as claimed in claim 17, wherein solution of the meso and micro structure in a solvent form suspension or gel upon acidification.

36) The process as claimed in claim 35, wherein the solution has a concentration of about 0.25 mg/ml to about 50 mg/ml, preferably about 2.5 mg/ml.

37) The process as claimed in claim 35, wherein the acidification is carried out by an organic acid.

38) The process as claimed in claim 37, wherein the organic acid is selected from a group comprising acetic acid, formic acid, trichloroacetic acid, dichloroacetic acid and trifluroacetic acid, preferably trifiuroacetic acid.

39) The process as claimed in claim 35, wherein the suspension is formed at an acid volume of about 2.5 μΐ to about 6.5 μΐ, and the gel is formed at an acid volume of about 11 μΐ to about 13 μΐ, preferably about 12 μΐ .

40) The process as claimed in claim 35, wherein the solution of meso and micro structure form nanostructures selected from a group comprising nanofibers, fibers, nanotubes and nanosheets.

41) A composition comprising a synthetic cyclic dipeptide which self assembles to form nano, meso and micro structures along with additives.

42) A composition comprising self assembled nano, meso and micro structure of synthetic cyclic dipeptide along with additives.

43) The composition as claimed in claims 41 and 42, wherein the dipeptide is obtained from a group comprising natural aromatic amino acids, unnatural aromatic amino acids, derivatives of amino acids and any combination thereof. 44) The composition as claimed in claim 42, wherein the amino acids are selected from a group comprising Phenylalanine, Phenylglycine and combination thereof.

45) The composition as claimed in claims 41 and 42, wherein the dipeptide is 3,6- dibenzylpiperazine.

46) The composition as claimed in claims 41 and 42, wherein the dipeptide is 3,6- dibenzylpiperazine-2-5-dione

47) The composition as claimed in claims 41 and 42, wherein the dipeptide is 3,6- diphenylpiperazine.

48) The composition as claimed in claims 41 and 42, wherein the dipeptide is 3,6- diphenylpiperazine-2,5-dione.

49) The composition as claimed in claims 41 and 42, wherein the additives are selected from a group comprising binders, disintegrants, diluents, lubricants, plastizers, permeation enhancers, solubilizers, preservatives, colouring agents, oxidizing agens, reducing agenets, pharmaceutical agents, nanoparticles, silica, hydroxyapatite, metal compositions, polymers, fibers and natural materials.

50) The composition as claimed in claim 42, wherein the nano, meso and micro structure is selected from a group comprising nanofibers, nanofiber bundles, fibers, fiber bundles, nanotubes, nanotube bundles, nanosheets, mesosheets, 2D sheets and gels.

51) A method of inhibiting fibrillization in neurodegenerative diseases, the method comprising act of contacting self assembled structure as claimed in claim 9, along with pharmaceutically acceptable additives in a subject in need thereof.

52) A method of cell culturing, the method comprising act of culturing cells in a nutrient medium along with meso and micro structures as claimed in claim 9 as template for differentiation of cells.

53) A method of using nano, meso and micro structures as claimed in claim 9 as optoelectronic component, the method comprising act of contacting the nano, meso and micro structure with an electronic device in need thereof.

54) A method of drug delivery, the method comprising act of delivering a predetermined drug in an envelop of nano, meso and micro structure as claimed in claim 9. 55) A method of using nano, meso, and micro structure as claimed in claim 9 as a biomaterial, the method comprising act of contacting the nano, meso and micro structure along with additives in a subject in need thereof.

56) The method as claimed in claim 55, wherein the biomaterial is selected from a group comprising composites, suture, fabric and bandage material.