MXPA99009106A

MXPA99009106A - Synthetic peptides useful in biological assays for detecting infections caused by group o hiv-1 viruses

Info

Publication number: MXPA99009106A
Application number: MXPA/A/1999/009106A
Authority: MX
Inventors: Marie Bernard Chenebaux Denis; Yves Rieunier Francois; Hubert Delagneau Jeanfrancoise; Jean Xavier Gadelle Stephane
Original assignee: Marie Bernard Chenebaux Denis; Delagneau Jeanfrancois Hubert; Jean Xavier Gadelle Stephane; Pasteur Sanofi Diagnostics; Yves Rieunier Francois
Priority date: 1997-04-09
Filing date: 1999-10-05
Publication date: 2000-06-05

Abstract

The invention concerns peptides used in biological assays for detecting infections caused by group O HIV-1 viruses, the method for preparing them, compositions and kits containing such peptides and the biological assays using such peptides.

Description

SYNTHETIC PEPTIDES USED IN BIOLOGICAL TESTING FOR THE DETECTION OF INFECTIONS DUE TO HIV-1 VIRUSES OF THE GROUP OR DESCRIPTION OF THE INVENTION The invention relates to synthetic peptides which can be used in biological tests or assays for the detection of infections due to group VIII HIV-1 viruses, their preparation procedure, compositions and equipment containing such peptides, and to the biological tests that put into operation such peptides. The HIV-1 retroviruses of group O are known in the prior art. European Patent EP-0,345,375 and European Patent Application EP-0,657,532 describe the isolates ANT 70 and ANT 70 NA isolated from Cameroonian patients. These documents describe more precisely the antigens and antigenic compositions containing the lysates or proteins of these isolates, the nucleic acids corresponding to the genomic RNA, the hybridization methods that put these nucleic acids into operation, the production methods of the isolates previously named, as well as the REF .: 31491 procedures for the preparation of the proteins pl2, plß, p25, gp41, gpl20 of these retroviruses. European application EP-0,591,914 describes the isolated MVP 5180/91. This isolate characterized by Western blotting present, as the previous isolate, differences in relation to isolates of the HIV-1 retrovirus known for a long time. The European application EP-0,591,914 describes precisely the DNA sequence of the isolate MVP 5180/91 and indicates precisely the location of the gag, pol and env genes. European application EP-0,591,914 describes even the synthetic peptides of the V3 loop or curl as well as the immunodominant region (gp41). The latter are useful for biological tests, mainly for the detection, in vi tro, of antibodies HIV-l of the group O. The European application EP-0,673,948 describes the synthetic or recombined peptides constituted from 15 to 50 amino acids (AA) and that include the sequence: -VWGIRQLRARLQALETLIQNQQRLNLWGXKGKLIXYTSVKWNTSWSGR- in which X represents either a cysteine residue or a serine residue. These peptides are useful in the diagnostic domain for the detection of infections due to certain HIV-1 group retrovirus isolates. European application EP-0,727,483 is also known, which describes the isolated MVP 2901/94 which is also part of the retroviruses belonging to the HIV-1 family of group 0. This application describes certain antigens that have well-determined peptide sequences. These peptide sequences correspond to a part of the sequence of the gpl20 and a part of the gp41 (immunodominant region) of the MVP 2901/94 isolate. International application WO 96/12809 describes two novel isolates belonging to the HIV-1 family of group 0. These are the VAU and DUR isolates. This application describes certain peptide sequences from two viruses mentioned above, useful for the detection of antibodies that recognize the HIV-1 VAU or DUR peptide sequences. International application WO 96/32293 describes two antigens from the sequence of the isolated ANT 70. It is the antigen called MDL061 and the antigen MDL056, from the immunodominant region of gp41. According to this invention, to detect 100% of the samples from a limited collection of sera from patients infected with the HIV-1 group 0 virus, it is necessary to use compositions containing these two peptides, since each isolated peptide does not allow for yes only to obtain satisfactory results. In fact, it is almost impossible, with respect to the genetic variability revealed by the isolates of the group 0 virus, to guarantee the early serological diagnosis of the contaminated individuals through the use of the antigens coming from it and the only isolated one. This means that it is not possible to obtain reagents that guarantee 100% sensitivity. Group 0 thus causes a major problem for the first time; it is the inadequacy of certain serological reagents to recognize individuals contaminated with particularly divergent groups or subtypes. This is the case precisely for HIV-1 of group O. International application WO 96/40763 also insists on the great divergence of group O. This application describes the peptides that incorporate, in a natural sequence HIV-1 of type B, some small modifications (replacing one or two amino acids). According to this application, these hybrid peptides are capable of reacting with the anti-group 0 antibodies. The application WO 96/27013 describes a series of novel HIV-1 group 0 viruses designated BCF 01, BCF 02, BCF 03, BCF 06, BCF 07, BCF 08, BCF 09, BCF 11, BCF 12, BCF 13 and BCF 14 as well as a series of peptides from the dominant region of the corresponding gp41 named ESS / BCF02, FAN / BCF01, LOB / BCF06, MAN / BCF07, NKO / BCF08, POC / BCF03, NAN / BCF11, BCF09, BCF12, BCF13 and BCF14. A certain number of these peptides are unmanageable in diagnosis because of their weak solubility, mainly the peptide BCF13. Unexpectedly, it has now been found that certain synthetic peptides are superior diagnostic reagents and allow to successfully screen infected patients with group VIII HIV-1 retroviruses. These peptides are composed of variable sequences articulated around short sequences. highly conserved, present in the isolates of the retroviral HIV-l group O. The peptides of the invention allow to obtain results much superior to those obtained with the synthetic peptides carrying immunodominant epitopes of the gp41 (env) of certain isolates of HIV-1 of the group 0. In the subsequent, to name the amino acids, the three-letter nomenclature will be used. The synthetic peptides of the invention correspond to the general formula (I):? -Z-TrpGlyCys-T-CysTyrThrSer-O (I) in which: -? represents a biotinyl radical, a biocytin radical, a hydrogen atom, an acetyl radical (CH3C0-), an aliphatic chain which may contain one or two thiol, aldehyde or amine functional groups, the aliphatic chain is preferably an alkyl chain of 1 to 6 carbon atoms or an alkenyl chain of 2 to 6 carbon atoms, or a chain of α-C6-carbonylcarbonyl, -Z represents a peptide sequence of one of formulas (II) to (X) ): - ?? - Ser-? 2- (II) -Ser-? 2- (III) -? 1 -Gln-? 2- (V) -Gln-? 2- (VI) ?? ~ Asn-? 2- (VI I I) Asn-? 2 - (IX) -Asr? - (X)CD. in which: -? i represents a peptide sequence of 0 to 9 amino acids and -? 2 represents a peptide sequence of 0 to 5 amino acids, T represents a peptide sequence of the formula (XI): - (AAi) - (AA2) - (AA3) - (AA4) - (AA5) - (XI) where: * (AA?) Represents either a lysine residue, or an arginine residue, or an ornithine residue, • (AA2) ) represents either a glycine residue, or an asparagine residue, (AA3) represents either a lysine residue, or an arginine residue, or an ornithine residue, • (AA) represents either a leucine residue, either an alanine residue, or an isoleucine residue, or a glutamine residue, • (AA5) represents either an isoleucine residue, a valine residue, or a leucine residue either a threonine residue, or a norleucine residue, or a norvaline residue, with the proviso that (AAi), (AA2), (AA3), (AA) and (AA5) never jointly form the peptide sequences -Lys Gly Lys Leu lie- and -Lys Gly Lys Leu Val-, -O, fixed on the -CO- group of serine represents: -a hydroxyl radical (-OH) or an amino radical (-NH2), an alkoxy radical including from 1 to 6 carbon atoms, -a peptide sequence of the formula (XII): -Val-S-? (XII) in which S represents a sequence of the formula (XIII) or of the formula (XIV): - (AAg) -Trp Asn- (AA7) - (AA8) (XIII) - (AA6) -Trp His- (AA7) - (AA8) (XIV) in which: • (AA6) represents an amino acid different from lysine, • (AA7) represents an amino acid, • (AA8) represents a serine or threonine residue, and? fixed on the residue -C0-of the free amino acid AA8, represents an OH group, NH2 or an alkoxy radical containing from 1 to 6 carbon atoms, -a peptide sequence of the formula (XV): -Val-? (XV) in which? fixed on the residue -CO- of the valine, has the same meaning as for the formula (XII), -or a peptide sequence of one of the formulas (XVI) to (XVIII): -Z-TrpGlyCys-T-CysTyrThrSer- ? (XVI) Val-S-Z-TrpGlyCys-T-CysTyrThrSerVal-S-? (XVII) Val-Z-TrpGlyCys-T-CysTyrThrSerVal-? (XVIII) in which Z and T have the definition given for formula (I) and S has the definition given for formula (XII) and? fixed on the residue of -CO- of the serine, on the residue -CO- of the amino acid AA8 or on the residue -CO- of the valine, has the same meaning as for the formula (XII).

When O represents a peptide sequence of one of formulas (XVI) to (XVIII), the peptide of formula (I) becomes a dimer, wherein the size may vary from 26 to 66 amino acids. When O does not represent a peptide sequence of one of the formulas a (XVI) to (XVIII), the peptides of the formula (I) are of the monomeric type and their size can vary from 13 to 33 amino acids. The peptides according to the invention can be either in the linear form or in the cyclized form by means of inter-cysteine disulphide bridges. Preferred are compounds of the formula (I) in which (AA5) represents either a valine residue, or a leucine residue, or a threonine residue, and when O corresponds to a peptide sequence of the formula ( XII), (AA6) represents either a glutamine residue, or an arginine residue. Preferred are the peptides of the formula (I) in which ': -? represents a biotinyl radical, a hydrogen atom, or an aliphatic chain which may contain one or two thiol, aldehyde or amine functional groups, the aliphatic chain is preferably an alkyl chain of 1 to 6 carbon atoms, or an aminoalkylcarbonyl chain of 2 to 6 carbon atoms, -Z represents a peptide sequence of the formula (II) or (V), in which? I represents a peptide sequence of two amino acids and? 2 represents an amino acid, or a sequence of the formula ( IV), in which? I represents three amino acids, or a peptide sequence of formula (VIII), in which? I represents a peptide sequence of nine, eight or three amino acids and? 2 a peptide sequence of five amino acids, - T represents a peptide sequence of the formula: -Lys Gly Arg Leu Val-, -Arg Gly Lys Ala Val-, -Arg Gly Arg Leu Val-, -Arg Gly Arg Ala Val-, and * -O represents a hydroxyl group, the peptide sequence (XV) or one of the following sequences corresponding to the peptide sequence of the formula (XII): -Val Arg Trp Asn Glu Thr- ? -Val Gln Trp Asn Glu Thr-? or -Val Gln Trp Asn Ser Thr- ?. Preferably Z represents a peptide sequence of the formula: • -Leu Leu Ser Ser- • -Leu Leu Asn Ser- • -Leu Leu Gln Ser- • -Arg Leu Asn Ser • -Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln c Leu Leu Asn Ser- • -Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asp Leu- • -Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asn Ile- • -Leu Asn Gln Gln Arg Leu Leu Asn Ser-o -Arg Ala Leu 'Glu Thr Leu Leu Asn Gln Gln Arg Leu Leu Asn Ser- They also form part of the invention, the synthetic peptides that include 20 to 50 amino acids and that respond to the formula (a):? - Za-TrpGlyCys-T-CysTyrThrSer-Oa (la) in which Za represents a radical of the formulas Ha a la Xa: ?? a-Ser-? 2a (Ha) -Ser-? 2a (Illa) -? la-Ser (IVa)? la-Gln-? 2a (Va) -Gln-? 2a (Way) ?? a-Asn -? a (Villa) -Asn-? 2a (IXa) - ?? to-Asn (Xa) in which: -? ia represents a peptide sequence of 1 to 5 amino acids and -? 2a an amino acid, -Oa represents a peptide sequence of the formula (XII), as defined for the formula (I), or a peptide sequence of the formula (XVIIa): Val-S-Za-TrpGlyCys-T-CysTyrThrSerVal-S-? (XVIIa) in which Za has the definition given for the formula (la) and?, T, S and? they have the same meaning as for formula (I). Preferred are the peptides of the formula (I) or (la) which include one of the following sequences (these peptides being of the dimer or monomer type, as defined above). The sequences are given according to the one- and three-letter nomenclatures: Sequence No. 1 -LLSLWGCRGKAVCYTSVQWNET -or -Leu Leu Ser Leu Trp Gly Cys Arg Gly Lys Wing Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr- 15 20 22 Sequence No. 2 -LLSLWGCRGRLVCYTSVQWNET -or -Leu Leu Ser Leu Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr- 15 20 22 Sequence No -LLSSWGCKGRLVCYTSVQWNET- -Leu Leu Being Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr Thr Ser Val Gln Trp Asn Glu Thr- 16 20 22 Sequence No. 4 -LLSSWGCKGRLVCYTSVQWNST -or -Leu Leu Ser Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Ser Thr- 15 20 22 Sequence No. 5 -LLQSWGCKGRLVCYTSVQWNST -or -Leu Leu Gln Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Ser Thr- 15 20 22 Sequence No -LLNSWGCRGKAVCYTSVQWNET -or -Leu Leu Ásn Ser Trp Gly Cys Arg Gly Lys Wing Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr- 15 20 22 Sequence No. 7 -LLSLWGCRGRAVCYTSVQWNET - Leu Leu Ser Leu Trp Gly Cys Arg Gly Arg Wing Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr- 15 20 22 Sequence No. 8 -LLSSWGCRGRLVCYTSVQWNET -or -Leu Leu Ser Ser Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr- 15 20 22 Sequence No -LLSSWGCKGRLVCYTS -or -Leu Leu Ser Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser- 15 Sequence No. 10 -LLNSWGCKGRLVCYTS -or -Leu Leu Asn Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr Thr Ser- 15 Sequence No. 11 -ALETLLQNQQLLNSWGCRGRLVCYTSVRWNET- O -Ala Leu Glu Thr Leu Gln Asn Gln Gln Leu Leu Asn Ser 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 15 20 25 Trp Asn Glu Thr- 30 Sequence No. 12 -ALETLLQNQQLLNIWGCRGRLVCYTSVRWNET- -Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asn He 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 15 20 25 Trp Asn Glu Thr- 30 Sequence No. 13 -ALETLLQNQQLLDLWGCRGRLVCYTSVRWNET -or -Ala Leu Glu Thr Leu Gln Asn Gln Gln Leu Leu Asp Leu 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 15 20 25 Trp Asn Glu Thr- 30 Sequence No. 14 -LNQQRLLNSWGCKGRLVCYTSV-o -Leu Asn Gln Gln Arg Leu Leu Asn Ser Trp Gly Cys Lys Gly 1 5 10 Arg Leu Val Cys Tyr Thr Ser Val-15 20 Sequence No. 15 -RALETLLNQQRLLNSWGCKGRLVCYTSV-o -Arg Ala Leu Glu Thr Leu Leu Asn Gln Gln Arg Leu Leu Asn 1 5 10 Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr Thr Ser Val-15 20 25 Sequence No. 16 -RLNSWGCKGRLVCYTSV- -Arg Leu Asn Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val-15 The following synthetic peptides are particularly preferred peptides: Peptide No. 1 (2B): SEQ ID No. 1 LLSLWGCRGKAVCYTSVQWNET or Leu Leu Ser Leu Trp Gly Cys Arg Gly Lys Wing Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 22 Peptide No. 2 (3B): SEQ ID No. 2 LLSLWGCRGRLVCYTSVQWNET or Leu Leu Ser Leu Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 22 Peptide No. 3 (4B): SEQ ID No. 3 LLSSWGCKGRLVCYTSVQWNET or Leu Leu Ser Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr Peptide No. 4 (5B): SEQ ID No. 4 LLSSWGCKGRLVCYTSVQWNST or Leu Leu Ser Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Ser Thr 15 20 22 Peptide No. 5 (6B): SEQ ID No. 5 LLQSWGCKGRLVCYTSVQWNST or Leu Leu Gln Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Ser Thr 15 20 22 Peptide No. 6: SEQ ID No. 6 LLNSWGCRGKAVCYTSVQWNET or Leu Leu Asn Ser Trp Gly Cys Arg Gly Lys Wing Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 22 Peptide No. 7: SEQ ID No. 7 LLSLWGCRGRAVCYTSVQWNET Leu Leu Ser Leu Trp Gly Cys Arg Gly Arg Ala Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 22 Peptide No. 8 (7B): SEQ ID No. LLSSWGCRGRLVCYTSVQWNET or Leu Leu Ser Ser Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 22 Peptide No. 9 (12B): SEQ ID No. 9 LLSSWGCKGRLVCYTS or Leu Leu Ser Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser 15 Peptide No. 10 (14B): SEQ ID No. 10 LLNSWGCKGRLVCYTS or Leu Leu Asn Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser 15 Peptide No. 11 (18B): SEQ ID No. 11 ALETLLQNQQLLNSWGCRGRLVCYTSVRWNET or Wing Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asn Ser 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 15 20 25 Trp Asn Glu Thr 30 Peptide No. 12 (19B): SEQ ID No. 12 ALETLLQNQQLLNIWGCRGRLVCYTSVRWNET or Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asn He 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 15 20 25 Trp Asn Glu Thr 30 Peptide No. 13 (20B): SEQ ID No. 13 ALETLLQNQQLLDLWGCRGRLVCYTSVRWNET or -Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asp Leu 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 15 20 25 Trp Asn Glu Thr 30 Peptide No. 14 (21B): SEQ ID No. 14 LNQQRLLNSWGCKGRLVCYTSV or Leu Asn Gln Gln Arg Leu Leu Asn Ser Trp Gly Cys Lys Gly 1 5 10 Arg Leu Val Cys Tyr Thr Ser Val 15 20 Peptide No. 15 (22B): SEQ ID No. 15 RALETLLNQQRLLNSWGCKGRLVCYTSV or Arg Ala Leu Glu Thr Leu Leu Asn Gln Gln Arg Leu Leu Asn 1 5 10 Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr Thr Ser Val 15 20 25 Peptide No. 16 (23B): SEQ ID No. 16 RLNSWGCKGRLVCYTSV Arg Leu Asn Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val 15 The synthetic peptides of the formula (I), object of the present invention, can be obtained by solid phase synthesis according to the classical methods: R.B. Merrifield, J. Amer. Ch em. Soc. (1963), 8_5, pp. 2149-2154; R.C. Sheppard, in "Pepti des 1971", Nesvadba H. (ed.) North Holl and, Ams terdam, pp. 111; E. Atherton and R.L. Sheppard, in < < Sol i d phase pepti de syn thesi s, a practi cal approach », IRL PRESS, (1989), Oxford Uni versi ty Pres s, p. 25-34. As an automatic synthesizer, you can use the synthesizer < < 9050 Plus Pep Synthesizer »by Millipore or an equivalent synthesizer. The solid support, used for the synthesis, must be compatible with the technique and chemistry used. For example, for a synthesis on the synthesizer "9050 Plus pep. Synthesizer", it is recommended to use a resin adapted for the technique called "continuous flow"; PEG PS resins meet these criteria. These supports are constituted by an arm ("spacer") based on polyethylene glycol (PEG) located between the functional group of the polystyrene spheres and the anchoring point of the first amino acid. The nature of this anchor point may vary according to the chosen C-terminal functional group. In the present case, different PEG-PS resins have been used.

The starting resin and the amino acids used as raw materials are commercially available products (PerSeptive-Biosystem, or Néosystem). For peptide synthesis, the following side chain protecting groups have been used: The temporary protection of the primary amine functional group at the amino acid position, used, is the 9-fluorenylmethyloxycarbonyl group (Fmoc). The deprotection is carried out by means of a 20% piperidine solution in dimethylformamide.

For coupling, an excess of diisopropylcarbodiimide (DIPCDI) and hydroxy-1-benzotriazole (HOBt) is preferably used. After the synthesis, the resin is washed with organic solvents, (dimethylformamide, then dichloromethane) dried under vacuum and then treated with a solution based on trifluoroacetic acid (TFA) cooled to 0 ° C and containing the "scrubbers" appropriate. For example, reagent K containing 82% trifluoroacetic acid, 5% phenol, 5% water, 5% thioanisole and 3% ethanedithiol can be used. After filtration of the resin, the synthetic peptides are precipitated and rinsed with ether. The synthetic peptides are then purified by reverse phase liquid chromatography and their purity is determined by mass spectrometry. As a solid phase, for example, the Bondapak C-18 phase can be used. The peptides are eluted by performing a linear gradient between two buffer solutions, the first being essentially aqueous (eg water-0.1% TFA) and the second organic mass (eg a mixture containing 60% acetonitrile, 39.92% water and trifluoroacetic acid). 0.08%). The collected pure fractions are collected, concentrated in vacuo and lyophilized. For cyclization, the purified synthetic peptides are dissolved in an ammonium acetate solution (10 mM). The pH is adjusted to 8.5 by the addition of 1 M ammonia. The solution is stirred vigorously. The cyclization is completed after 18 hours. The pH is then lowered to 6 by the addition of acetic acid. The cyclized peptides are lyophilized, then purified by reverse phase liquid chromatography as described above. The immunoreactivity of the peptides of the invention has been evaluated with the help of sera from patients of Cameroonian origin infected with retroviruses HIV-l of group 0. The different tests carried out have shown that the peptides of the invention, alone or in combination (compositions of peptides), allow to detect 100% of the sera infected with the HIV-l retrovirus of group 0. The synthetic peptides of the invention find their application in the immunological tests for the follow-up or detection of infections due to the HIV-1 retroviruses of the group O. It is also possible to use combinations of several synthetic peptides of the formula I. These associations, which may have two or more peptides of the formula I, also form part of the invention. Associations containing the peptides No. 1 (2B) and No. 3 (4B) are preferred. It is also possible to use the synthetic peptides of the formula (I) of the present invention in association with recombinant peptides (recombinant proteins) HIV-1 of the group O such as can be obtained by the classical methods and having the sequences described for example in European application EP-0, 591, 914. Such compositions also fall within the scope of the present invention. The synthetic peptides of the invention can also be used in association with other synthetic peptides or recombined with HIV-1. (recombinant proteins) and / or HIV-2, such as the peptides described in European patent applications or patents EP-0, 387, 914, EP-0, 239, 425, EP-0,220,273, or EP-0, 267 , 802. This list of patent applications, or patents is not exhaustive and is given as an example. The compositions containing one or several synthetic peptides of the formula (I) and one or more synthetic or recombinant peptides HIV-1 or HIV-2 find their application in diagnosis for the early detection of patients infected with different HIV retroviruses. These compositions also form part of the present invention. Immunosupication procedures using one or more synthetic peptides of the formula (I), alone or in association with the recombined peptides HIV-1 of the group O or the synthetic or recombined peptides HIV-1 and / or HIV-2, also form part of the invention. The invention also contemplates the equipment for the operation of immuno-dilutions, which include a peptide of the formula (I) or a composition containing at least one peptide of the formula (I). The following examples illustrate the invention and are given in a non-limiting manner.

EXAMPLE 1 Preparation of a compound according to the invention; Peptide No. 2 (3B) LLSLWGCRGRLVCYTSVQWNET or Leu Leu Ser Leu Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 22 This peptide has been synthesized in solid phase. The technique developed in 1963 by Merrifield (J. Am. Chem. Soc (1963) 8_5, pp. 2149-2154) consists of fixing the first amino acid on a solid polymeric support (resin) by its functional group and lengthening the peptide sequence from this first amino acid, leaving the peptide in the process of synthesis anchored on the resin. For the synthesis of peptide No. 2, the synthesizer "9050 Plus Pep Synthetizer" and, as resin, the resin Fmoc Thr (OtBu) PEG PS have been used as the synthesizer. The different stages of the synthesis are summarized in the following Table I: Table I RESIDUE OF PROTECTION PROTECTION METHOD OF NUMBER OF EQ-AMINOACIDO NH2 LATERAL COUPLING DURATION OF COUPLING Glu Fmoc OtBu DIPCDI / HOBt 5 eq-30 min Asn Fmoc Trt DIPCDI / HOBt 5 eq-30 min Trp Fmoc Boc DIPCDI / HOBt 5 eq-30 min Gln Fmoc Trt DIPCDI / HOBt 5 eq-30 min Val Fmoc DIPCDl / HOBt 5 eq-30 min Be Fmoc tBu DIPCDl / HOBt 5 eq-30 min Thr Fmoc tBu DIPCDI / HOBt 5 eq-30 min Tyr Fmoc tBu DIPCDl / HOBt 5 eq-30 min Cys Fmoc Trt DIPCDl / HOBt 5 eq-30 min Val Fmoc DIPCDl / HOBt 5 eq-30 min Leu Fmoc DIPCDl / HOBt 5 eq-30 min Arg Fmoc Pbf DIPCDl / HOBt 5 eq-30 min Gly Fmoc DIPCDl / HOBt 5 eq-30 min Arg Fmoc Pbf DIPCDl / HOBt 5 eq-30 min Cys Fmoc Trt DIPCDl / HOBt 5 eq-30 min Gly Fmoc DIPCDl / HOBt 5 eq-30 min Trp Fmoc Boc DIPCDl / HOBt 5 eq-30 min Leu Fmoc DIPCDl / HOBt 5 eq-30 min Be Fmoc tBu DIPCDl / HOBt 5 eq-30 min After the end of the synthesis, the resin is washed with dimethylformamide, and then with dichloromethane and dried under vacuum. Next, the resin is treated with reagent K (82% trifluoroacetic acid, 5% phenol, 5% water, 5% thioanisole, 3% ethanedithiol). Peptide No. 2 (3B) is isolated by precipitation with the aid of diethyl oxide, and is then rinsed with the same solvent. 140 mg of peptide No. 2 (3B) is thus obtained. Peptide No. 2 (3B) was then purified by reverse phase liquid chromatography. As a solid phase, the Bondapac C-18 phase was used. The peptide was eluted by performing a linear gradient in two buffer solutions, the first being essentially aqueous (for example water-0.1% TFA) and the second more organic (for example, a mixture containing: 60% acetonitrile, 39.92% water and 0.08% TFA). The collected pure fractions were then pooled, concentrated in vacuo and lyophilized.

For cyclization, the purified synthetic peptide, obtained in this way was dissolved in a solution of ammonium acetate (10 M). The pH was adjusted to 8.5 by the addition of ammonia ÍM. The solution was vigorously agitated. The cyclization was completed after 18 hours. The pH was then lowered to 6 by the addition of acetic acid. The cyclized peptide was lyophilized, then purified by reverse phase liquid chromatography as described above.

Preparation of a compound according to the invention: Peptide No. 15 (22B) This peptide was synthesized as peptide No. 2 (3B), but using as resin, the FmocPAL PEG-PS resin. The different stages of the synthesis are summarized in the following Table II: Table II RESIDUE OF PROTECTION PROTECTION METHOD OF NUMBER OF EQ-AMINOACIDO NH2 LATERAL COUPLING DURATION OF COUPLING Val Fmoc DIPCDl / HOBt 5 eq-45 min Be Fmoc tBu DIPCDl / HOBt 5 eq-45 min Thr Fmoc tBu DIPCDl / HOBt 5 eq-45 min Tyr Fmoc tBu DIPCDl / HOBt 5 eq-45 min Cys Fmoc Trt DIPCDl / HOBt 5 eq-45 min Val Fmoc DIPCDl / HOBt 5 eq-45 min Leu Fmoc DIPCDl / HOBt 5 eq-45 min Arg Fmoc Pbf DIPCDl / HOBt 5 eq-45 min Gly Fmoc DIPCDl / HOBt 5 eq-45 min Lys Fmoc BOC DIPCDl / HOBt 5 eq-45 min Cys Fmoc Trt DIPCDl / HOBt 5 eq-45 min Gly Fmoc DIPCDl / HOBt 5 eq-45 min Trp Fmoc Boc DIPCDl / HOBt 5 eq-45 min Be Fmoc tBu DIPCDl / HOBt 5 eq-45 min Asn Fmoc Trt DIPCDl / HOBt 5 eq-45 min Leu Fmoc DIPCDl / HOBt 5 eq-45 min Leu Fmoc DIPCDl / HOBt 5 eq-45 min Arg Fmoc Pbf DIPCDl / HOBt 5 eq-45 min Gln Fmoc Trt DIPCDl / HOBt 5 eq-45 min Gln Fmoc Trt DIPCDl / HOBt 5 e q- 45 min Asn Fmoc Trt DIPCDl / HOBt 5 e q- 4 5 min Leu Fmoc DIPCDl / HOBt 5 eq-45 min Leu Fmo c DIPCDl / HOBt 5 eq- 45 min Thr Fmoc tBu DIPCDl / HOBt 5 e q- 45 min Glu Fmoc OtBu DIPCDl / HOBt 5 eq- 45 min Leu Fmoc DIPCDl / HOBt 5 eq- 45 min Al a Fmo c DIPCDl / HOBt 5 eq- 45 min Arg Fmoc Pb f DIPCDl / HOBt 5 eq- 4 5 min After the end of the synthesis, the resin was washed with dimethylformamide, then with dichloromethane and dried in vacuo. Then, the resin was treated with reagent K (82% trifluoroacetic acid, 5% phenol, 5% water, 5% thioanisole, 3% ethanedithiol). The peptide no. 15 (22B) was isolated by precipitation with the aid of diethyl oxide, and was immediately rinsed with the same solvent. 140 mg of peptide No. 15 (22B) was thus obtained. Peptide No. 15 (22B) was then purified by reverse phase liquid chromatography, then cyclized, lyophilized and purified as described above for peptide No. 2 (3B) Equivalently, and using the appropriate resins and amino acids, the other compounds of the invention were synthesized. Table III indicates the molecular weight of certain peptides of the formula (I), in the non-cyclized form, evaluated by mass spectrometry.

Table III EXAMPLE 2: Evaluation of the immunoreactivity of the peptides according to the invention by means of the immunoenzymatic test: Test No. 1 The sera used ESS, DUR, VAU and HAD are sera of French patients infected with retroviruses HIV-l group O. The other samples of sera from patients infected with retroviruses HIV-1 group O were obtained by the Pasteur Center of Yaunde in Cameroon and have been serotyped as OR groups according to the serological algorithm described in AIDS (1977), _H, pp. 445-453. HIV negative sera (n = 48) were obtained from healthy volunteers. The synthetic peptides used were dissolved in water at a concentration of 1 mg / ml (stock solution). For the sensitization step of the solid phase (coating), 110 μl of a 2 μg / ml solution of each peptide (obtained by diluting the stock solution with microtitre microtitre plates (NUNC) was added to each dome of the microtiter plates. the carbonate buffer solution O.lM). After overnight incubation at room temperature, the microplates were first washed with a Tris NaCl buffer solution pH 7.4, which contained 0.1% Tween® 20 and 0.001% sodium mertiolate, then saturated with a PBS solution containing 0.5% Régilait ™ (skimmed milk powder). After aspiration of the saturation solution, the plates were heated for 10 minutes at 50 ° C. The samples of the sera were diluted to 1/5 with a solution of skim milk (citrate buffer added with 0.01% phenol red, with 0.25% chloroform and with Kathon® al 0. 25%), deposited on the domes of the plates and placed to incubate for 30 minutes at 40 ° C. After washing with a buffer solution of Tris NaCl pH 7.4 containing 0.1% Tween® and 0.001% sodium mertiolate, 100 μl of a conjugated horse anti-IgG antibody solution was added to each plate dome. Human IgM labeled with horseradish peroxidase, containing as preservative 0.01% sodium merthiolate, in solution in a buffer solution of citrate added with 30% glycerol and 25% normal fetal calf serum, then the plates were placed incubate for 30 minutes at 40 ° C.

After washing with a buffer solution Tris NaCl pH 7.4 containing 0.1% Tween and 0.001% sodium mertiolate, the development of the coloration was obtained by adding, in each dome, 100 μl of O-phenylenediamine in solution in hydrogen peroxide. The microplates were then placed to incubate for 30 minutes at room temperature and in the dark. The colored reaction was then stopped by addition of 100 μl of 4N sulfuric acid. Absorbance (A) was determined at 490 and 620 nm. The relative absorbance (A490-A620) related in each dome is proportional to the immunoreactivity of each peptide. This indicates the ability of each peptide to react with the biological sample with which the assay is performed. The value alone (cut) has been determined as an absorbance equal to 0.15. This corresponds to the mean of the negative values (n = 48) plus 12 standard deviations. The reactivity of the peptides of the invention (peptide No. 3 (4B), peptide No. 2 (3B) and peptide No. 1 (2B) all under the cyclized form) has been compared to that of two synthetic peptides having as sequence a part of the natural envelope sequence (env) of the isolate VAU (retroviruses HIV-1 group O) and including an immunodominant epitope of gp41. These two peptides have the following sequence: VAU 22 AA Leu Leu Asn Leu Trp Gly Cys Lys Asn Arg Wing He Cys Tyr 1 5 10 Thr Ser Val Lys Trp Asn Lys Thr 15 20 22 VAU 35 AA Arg Leu Leu Ala Leu Glu Thr Phe He Glu Glu Asn Glu Leu 1 5 10 Leu Asn Leu Trp Gly Cys Lys Asn Arg Wing He Cys Tyr Thr 15 20 25 Ser Val Lys Trp Asn Lys Thr 30 35 For the study, these peptides were used in the cyclized form. The results of this study are indicated in Table IV.

Table IV * serotypes / genotypes ** > = signal greater than the reading capacity of the spectrophotometer Table IV (continued) * serotypes / genotypes ** > = signal higher than the reading capacity of the spectrophotometer *** Not tested The results of Table IV demonstrate that peptide No. 3 (4B) has the best performances with respect to those obtained for the other peptides. This peptide allows the best discrimination of the sera of the patients infected with HIV-1 retroviruses of group O with respect to two peptides that have a part of the sequence of the VAU isolate corresponding to the immunodominant epitope of gp41. On the other hand, the peptides No. 2 (3B) and No. 1 (2B) of the invention are more immunoreactive than the peptide VAU 22 AA which includes the same number of amino acids.

EXAMPLE 3: Evaluation by immunoenzymatic test of the immunoreactivity of the peptides according to the invention: Test No. 2 Serum samples from patients infected with HIV-1 retroviruses of group O were obtained by the Pasteur Center of Yaunde in Cameroon and have been serotyped as group O according to the serological algorithm described in AIDS (1977), 1, 1, p. 445-453. A sample (Maryland) genotyped comes from the United States. These samples were previously diluted in human serum negative at the dilutions given in Table V, in order to deposit a sufficient volume for the different immunoreactivity assays.

The synthetic peptides used were dissolved in water at a concentration of 1 mg / mg (mother solution). For the stage of sensitization of the solid phase ("coating"), we proceeded as described for Example 2. The samples of sera were diluted to 1/5 with a solution of skim milk (in citrate buffer added with 0.01% phenol red, 0.25% chloroform, and 0.25% Kathon), deposited in the plate domes and placed "to incubate for 30 minutes at 40 ° C. After washing with a Tris NaCl buffer solution containing pH 7.4 0.1% Tween® 20 and 0.001% sodium mertiolate, 100 μl of horseradish peroxidase-labeled horse anti-human IgM and IgM horseradish antibody conjugate solution were added to each plate dome. 0.01% sodium mertiolate, in solution in a buffer solution of citrate added with 30% glycerol and with normal serum of 25% fetal calf, then these plates were put to incubate for 30 minutes at 40 ° C. washed, a buffer solution Tris NaCl pH 7.4 containing 0.1% Tween® 20 and 0.001% sodium mertiolate, the development of the coloration was obtained as already discovered in Example 2. The relative absorbance (OD) (A490-A620) bound in each dome is proportional to the immunoreactivity of each peptide. This indicates the ability of each peptide to react with the biological sample with which the assay is performed. The reactivity of the peptides of the invention, peptides No. 10 (14B), No. 11 (18B), No. 12 (19B), No. 14 (21B), No. 15 (22B), No. 16 (23B) ) all under the cyclized form, was compared that of three homologous synthetic peptides, which have as a sequence a part of the natural envelope sequence (env) of the HIV-l retrovirus of group O. These peptides are two peptides derived from the isolated VAU , -the peptide VAU 22 AA and the peptide VAU 35 AA- and the peptide MVP 5180 (designated "MVP 5180" in Table V). The VAU 22 AA and VAU 35 AA peptides (whose structure is indicated in Example 2) and the MVP 5180 peptide include an immunodominant epitope of gp41. All these peptides were used in the cyclized form. The sequence of peptide MVP 5180 is as follows: MVP 5180 Arg Leu Gln Ala Leu Glu Thr Leu He Gln Asn Gln Gln Arg 1 5 10 Leu Asn Leu Trp Gly Cys Lys Gly Lys Leu He Cys Tyr Thr 15 20 25 Ser Val Lys Trp Asn Thr Ser 30 35 The results of this study are indicated in Table V.

Table V SOLID PHASE *: PEPTIDO 2 μg / ml For each peptide tested, the samples were classified into four classes (a, b, c, and d) corresponding to various levels of relative absorbance linked to the wavelengths A492-A620: • - for a: DO < 0.100, • - for b: 0.100 < DO < 0,500, • - for c: 0,500 < DO < 1,000, • - for d: DO > 1, 000, thus allowing to evaluate the degree of immunoreactivity of the peptides. The most immunoreactive peptides are those for which the largest number of samples is found in the classes corresponding to the highest absorbances.

The results are indicated in Table VI Table VI SOLID PHASE *: PEPTIDO 2 μg / ml The results show that all the peptides of the invention tested perform a better function in immunoreactivity than the reference peptides of the prior art which are derived from the natural isolates (MVP 5180, VAU). The peptides of the invention No. 15 (22B), No. 14 (21B), and No. 16 (23B) prove to be the most immunoreactive.

E JEMPLO 4 Evaluation of the immunoreactivity of the compositions containing peptides according to the invention by immunoenzymatic test For this test, we proceeded according to the protocol described in Example 2 and the same sera were used. The microplates used were sensitized with either the cyclized peptide No. 1 (2B), either with cyclized peptide No. 3 (4B), or with a composition containing these two peptides (1: 1 w / w). In each dome were deposited, either 100 μl of a solution containing 2 μg / ml of peptide No. 1 (2B), or 100 μl of a solution containing 2 μg / ml of peptide No. 3 (4B), or 100 μl of a solution containing 1 μg / ml of peptide No. 1 (2B) and 1 μg / ml of peptide No. 3 (4B). The results of this test are given in the Table VII.

Table VII > = signal higher than the reading capacity of the spectrophotometer.

Table VII (continued) > = signal higher than the reading capacity of the spectrophotometer.

The results of Table VII demonstrate that the compositions of the peptides of the invention, when used in diagnosis, allow the detection of all sera from patients infected with HIV-1 retroviruses of group O.

LIST OF SEQUENCES 1) GENERAL INFORMATION: i) APPLICANT: (A) NAME: Pasteur Sanofi Dagnostics (B) STREET: 3 boulevard Raymond Poincaré (C) CITY: Marnes la Coquette (E) COUNTRY: France (F) POSTAL CODE: 92430 (G) TELEPHONE: 0153774000 (H) FAX: 0153774133 ii) TITLE OF THE INVENTION: Synthetic peptides usable in biological tests for the detection of infections due to the HIV-1 virus of group O iii) SEQUENCE NUMBER: 16 iv) COMPUTER LEGIBLE FORM: (A) TYPE OF MEDIA: Flexible disk (B) COMPUTER: IBM compatible PC (C) OPERATING SYSTEM: PC-DOS / MS-DOS (D) SOFTWARE: Patentln Relay # 1.0, Version # 1.25 (OEB) 2) INFORMATION FOR SEQ ID NO. 1: i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 22 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. 1: Leu Leu Ser Leu Trp Gly Cys Arg Gly Lys Wing Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 2) INFORMATION FOR SEQ ID NO. 2: i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 22 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. 2: Leu Leu Ser Leu Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 2) INFORMATION FOR SEQ ID NO. 3: i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 22 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO Leu Leu Ser Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 2) INFORMATION FOR SEQ ID NO. 4: i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 22 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. 4: Leu Leu Be Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Ser Thr 15 20 2) INFORMATION FOR SEQ ID NO. 5: CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 22 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. 5: Leu Leu Gln Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Ser Thr 15 20 2) INFORMATION FOR SEQ ID NO. 6: i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 22 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. 6: Leu Leu Asn Ser Trp Gly Cys Arg Gly Lys Wing Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 2) INFORMATION FOR SEQ ID NO. 7: i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 22 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. 7: Leu Leu Ser Leu Trp Gly Cys Arg Gly Arg Wing Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 2) INFORMATION FOR SEQ ID NO. 8: i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 22 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. 8: Leu Leu Be Ser Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 2) INFORMATION FOR SEQ ID NO. 9: i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 16 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. 9: Leu Leu Ser Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser 15 2) INFORMATION FOR SEQ ID NO. 10: CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 16 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. 10: Leu Leu Asn Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser 15 2) INFORMATION FOR SEQ ID NO. eleven: i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 32 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. eleven: Wing Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asn Ser 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 15 20 25 Trp Asn Glu Thr 30 INFORMATION FOR SEQ ID NO. 12 CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 32 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. 12: Wing Leu Glu Thr Leu Gln Asn Gln Gln Leu Leu Asn He Trp 1 5 10 15 Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg Trp 20 25 Asn Glu Thr 30 2) INFORMATION FOR SEQ ID NO. 13: i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 32 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. 13 Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asp Leu 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 20 25 Trp Asn Glu Thr 30 2) INFORMATION FOR SEQ ID NO. 14: i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 22 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide -xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. 14: Leu Asn Gln Gln Arg Leu Leu Asn Ser Trp Gly Cys Lys Gly 1 5 10 Arg Leu Val Cys Tyr Thr Ser Val 15 20 2) INFORMATION FOR SEQ ID NO. fifteen: i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 28 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. fifteen: Arg Ala Leu Glu Thr Leu Leu Asn Gln Gln Arg Leu Leu Asn 1 5 10 Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr Thr Ser Val 15 20 25 2) INFORMATION FOR SEQ ID NO. 16: i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 17 amino acids (B) TYPE: amino acid ii) TYPE OF MOLECULE: peptide xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO. 16 Arg Leu Asn Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val 15 It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Having described the invention as above, the content of the following claims is claimed as property:

Claims

1. The synthetic peptides of the monomeric type of 13 to 33 amino acids or of the dimeric type of 26 to 66 amino acids, under the linear form or under the cyclized form, by means of inter-cysteine disulfide bridges, corresponding to the general formula (I): ? -Z-TrpGlyCys-T-CysTyrThrSer-O (I) characterized by: -? represents a biotinyl radical, a biocytin radical, a hydrogen atom, an acetyl radical (CH3CO-), an aliphatic chain which may contain one or two thiol, aldehyde or amine functional groups, the aliphatic chain is preferably an alkyl chain of 1 to 6 carbon atoms or an alkenyl chain of 2 to 6 carbon atoms, or an aminoalkylcarbonyl chain of 2 to 6 carbon atoms, -Z represents a peptide sequence of one of formulas (II) to (X) : -??-Be-? - (II) -Ser-? 2- (III) - ?? - Gln-? 2- (V) Gln-? 2- (VI)? ~ Asn-? 2- (VI II) Asn-? 2- (IX) 7-Asn- (X) wherein: • -? i represents a peptide sequence of 0 to 9 amino acids and -? 2 represents a peptide sequence of 0 to 5 amino acids, T represents a peptide sequence of the formula (XI): - (AAi) - (AA2 ) - (AA3) - (AA4) - (AA5) - (XI) in which: • (AAi) represents either a lysine residue, either an arginine residue, or an ornithine residue, • (AA2) ) represents either a glycine residue, or an asparagine residue, • (AA3) represents either a lysine residue, or an arginine residue, or an ornithine residue, • (AA4) represents either a leucine residue, either an alanine residue, or an isoleucine residue, or a glutamine residue, • (AA5) represents either an isoleucine residue, a valine residue, or a leucine residue either a threonine residue, or a norleucine residue, or a norvaline residue, with the condition nevertheless that (AAi), (AA2), (AA3), (AA) and (AA5) never jointly form the peptide sequences -Lys Gly Lys Leu He- and -Lys Gly Lys Leu Val-, -O, fixed on the -CO- group of serine represents: -a hydroxyl radical (-OH) or an amino radical (-NH2), an alkoxy radical including from 1 to 6 carbon atoms, -a peptide sequence of the formula (XII): -Val-S-? (XII) in which S represents a sequence of the formula (XIII) or of the formula (XIV): - (AA6) -Trp Asn- (AA7) - (AA8) (XIII) - (AA6) -Trp His- (AA7) - (AA8) (XIV) in which: • (AA6) represents an amino acid different from lysine, • (AA7) represents an amino acid, • (AA8) represents a serine or threonine residue, and? fixed on the residue -C0-of the free amino acid AA8, represents an OH group, NH2 or an alkoxy radical containing from 1 to 6 carbon atoms, -a peptide sequence of the formula (XV): -Val-? (XV) in which? fixed on the residue -CO- of the valine, has the same meaning as for the formula (XII), -or a peptide sequence of one of the formulas (XVI) to (XVIII): -Z-TrpGlyCys-T-CysTyrThrSer- ? (XVI) Val-S-Z-TrpGlyCys-T-CysTyrThrSerVal-S-? (XVII) Val-Z-TrpGlyCys-T-CysTyrThrSerVal-? (XVIII) in which Z and T have the definition given for formula (I) and S has the definition given for formula (XII) and? fixed on the residue of -CO- of the serine, on the residue -CO- of the amino acid AAs or on the residue -CO- of the valine, has the same meaning as for the formula (XII).

2. The synthetic peptides of the formula (I) according to claim 1, characterized in that (AA5) represents either a valine residue, or a leucine residue, or a threonine residue and when O corresponds to a peptide sequence of the formula (XII) or (XIV), (AA6) represents either a glutamine residue, or an arginine residue.

3. The synthetic peptides of the formula (I), according to claim 1, characterized in that: -? represents a biotinyl radical, a hydrogen atom, or an aliphatic chain that may contain one or two thiol functional groups, aldehyde or amine, the aliphatic chain is preferably an alkyl chain of 1 to 6 carbon atoms, or an aminoalkylcarbonyl chain of 2 to 6 carbon atoms, -Z represents a peptide sequence of the formula (II) or (V) , in which? i represents a peptide sequence of two amino acids and? 2 represents an amino acid, or a sequence of formula (IV), in which? i represents three amino acids, or a peptide sequence of formula (VIII), wherein? i represents a peptide sequence of nine, eight or three amino acids and? 2 a peptide sequence of five amino acids, -T represents a peptide sequence of the formula: -Lys Gly Arg Leu Val-, -Arg Gly Lys Ala Val -, -Arg Gly Arg Leu Val-, -Arg Gly Arg Ala Val-, -O represents a hydroxyl group, the peptide sequence (XV) or one of the following sequences corresponding to the peptide sequence of the formula (XII): -Val Arg Trp Asn Glu Thr-? -Val Gln Trp Asn Glu Thr-? or -Val Gln Trp Asn Ser Thr- ?.

4. The synthetic peptides of the formula (I), according to any of claims 1 to 3, characterized in that Z represents a peptide sequence of the formula: • -Leu Leu Ser Ser- • -Leu Leu Asn Ser- • -Leu Leu Gln Ser- • -Arg Leu Asn Ser- • -Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asn Ser- • -Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asp Leu- • -Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asn Ile- • -Leu Asn Gln Gln Arg Leu Leu Asn Ser-o -Arg Ala Leu Glu Thr Leu Leu Asn Gln Gln Arg Leu Leu Asn Ser-

5. Synthetic peptides from 20 to 50 amino acids according to claim 1, of formula (Ia): [alpha] -Za-TrpGlyCys-T-CysTyrThrSer-Oa (la) in which Za represents a radical of the formulas Ha a la Xa:? Xa-Ser- 2a (Ha) -Ser-? 2a (Illa) - ?? to-Ser (IVa)? La-Gln-? 2a (Va) -Gln-? 2a (Way) üla "Asn- £ l2a (Villa) - Asn-? 2a (IXa) in which: -? Ia represents a peptide sequence of 1 to 5 amino acids and - 2a an amino acid, -Oa represents a peptide sequence of the formula (XII), as defined for the formula (I), or a peptide sequence of the formula (XVIIa): Val-S-Za-TrpGlyCys-T-CysTyrThrSerVal-S-? (XVI la) ?, T, S and? they have the same meaning as for formula (I).

6. The synthetic peptides of the formula (I) according to any of claims 1 to 5, characterized in that they include the following sequences: Sequence No. 1 -LLSLWGCRGKAVCYTSVQWNET -or -Leu Leu Ser Leu Trp Gly Cys Arg Gly Lys Wing Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr- 15 20 22 Sequence No. 2 -LLSLWGCRGRLVCYTSVQWNET -or -Leu Leu Ser Leu Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr- 15 20 22 Sequence No. 3 -LLSSWGCKGRLVCYTSVQWNET- O -Leu Leu Ser Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr- 16 20 22 Sequence No. 4 -LLSSWGCKGRLVCYTSVQWNST- O -Leu Leu Ser Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Ser Thr- 15 20 22 Sequence No. 5 -LLQSWGCKGRLVCYTSVQWNST -or • -Leu Leu Gln Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Ser Thr- 15 20 22 Sequence No. 6 -LLNSWGCRGKAVCYTSVQWNET -or -Leu Leu Asn Ser Trp Gly Cys Arg Gly Lys Wing Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr- 15 20 22 Sequence No. 7 -LLSLWGCRGRAVCYTSVQWNET -or -Leu Leu Ser Leu Trp Gly Cys Arg Gly Arg Wing Val Cys Tyr 1. 5 10 Thr Ser Val Gln Trp Asn Glu Thr- 15 20 22 Sequence No -LLSSWGCRGRLVCYTSVQWNET - Leu Leu Ser Ser Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr- 15 20 22 Sequence No -LLSSWGCKGRLVCYTS- -Leu Leu Ser Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser- 15 Sequence No. 10 -LLNSWGCKGRLVCYTS -or -Leu Leu Asn Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser- 15 Sequence No. 11 -ALETLLQNQQLLNSWGCRGRLVCYTSVRWNET -or -Ala Leu Glu Thr Leu Gln Asn Gln Gln Leu Leu Asn Ser 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 15 20 25 Trp Asn Glu Thr- 30 Sequence No. 12 -ALETLLQNQQLLNIWGCRGRLVCYTSVRWNET-o -Ala Leu Glu Thr Leu Gln Asn Gln Gln Leu Leu Asn He 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 15 20 25 Trp Asn Glu Thr- 30 Sequence No. 13 -ALETLLQNQQLLDLWGCRGRLVCYTSVRWNET-o -Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asp Leu 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 15 20 25 Trp Asn Glu Thr- 30 Sequence No. 14 -LNQQRLLNSWGCKGRLVCYTSV-o -Leu Asn Gln Gln Arg Leu Leu Asn Ser Trp Gly Cys Lys Gly 1 5 10 Arg Leu Val Cys Tyr Thr Ser Val-15 20 Sequence No. 15 -RALETLLNQQRLLNSWGCKGRLVCYTSV- -Arg Ala Leu Glu Thr Leu Leu Asn Gln Gln Arg Leu Leu Asn 1 5 10 Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr Thr Ser Val-15 20 25 Sequence No. 16 -RLNSWGCKGRLVCYTSV- O -Arg Leu Asn Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val-15

7. The synthetic peptides according to any of claims 1 to 6, sequence: Peptide No. 1 (2B): LLSLWGCRGKAVCYTSVQWNET or Leu Leu Ser Leu Trp Gly Cys Arg Gly Lys Wing Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 22 Peptide No. 2 (3B) LLSLWGCRGRLVCYTSVQWNET O Leu Leu Ser Leu Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 22 Peptide No. 3 (4B) LLSSWGCKGRLVCYTSVQWNET or Leu Leu Ser Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 22 Peptide No. 4 (5B) LLSSWGCKGRLVCYTSVQWNST O Leu Leu Ser Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Ser Thr 15 20 22 Peptide No. 5 (6B) LLQSWGCKGRLVCYTSVQWNST or Leu Leu Gln Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Ser Thr 15 20 22 Peptide No LLNSWGCRGKAVCYTSVQWNET or Leu Leu Asn Ser Trp Gly Cys Arg Gly Lys Wing Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 22 Peptide No. 7: LLSLWGCRGRAVCYTSVQWNET or Leu Leu Ser Leu Trp Gly Cys Arg Gly Arg Wing Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 22 Peptide No (7B; LLSSWGCRGRLVCYTSVQWNET O Leu Leu Be Being Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val Gln Trp Asn Glu Thr 15 20 22 Peptide No. 9 (12B) LLSSWGCKGRLVCYTS O Leu Leu Ser Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser 15 Peptide No. 10 (14B) LLNSWGCKGRLVCYTS or Leu Leu Asn Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser 15 Peptide No. 11 (18B): ALETLLQNQQLLNSWGCRGRLVCYTSVRWNET or Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asn Ser 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 15 20 25 Trp Asn Glu Thr 30 Peptide No. 12 (19B): ALETLLQNQQLLNIWGCRGRLVCYTSVRWNET or Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asn He 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 15 20 25 Trp Asn Glu Thr 30 Peptide No. 13 (20B) ALETLLQNQQLLDLWGCRGRLVCYTSVRWNET or -Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Asp Leu 1 5 10 Trp Gly Cys Arg Gly Arg Leu Val Cys Tyr Thr Ser Val Arg 15 20 25 Trp Asn Glu Thr 30 Peptide No. 14 (21B): LNQQRLLNSWGCKGRLVCYTSV O Leu Asn Gln Gln Arg Leu Leu Asn Ser Trp Gly Cys Lys Gly 1 5 10 Arg Leu Val Cys Tyr Thr Ser Val 15 20 Peptide No. 15 (22B): RALETLLNQQRLLNSWGCKGRLVCYTSV or Arg Ala Leu Glu Thr Leu Leu Asn Gln Gln Arg Leu Leu Asn 1 5 10 Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr Thr Ser Val 15 20 25 Peptide No. 16 (23B): RLNSWGCKGRLVCYTSV or Arg Leu Asn Ser Trp Gly Cys Lys Gly Arg Leu Val Cys Tyr 1 5 10 Thr Ser Val 15

8. A composition, characterized in that it contains one or more synthetic peptides of the formula (I) according to any of claims 1 to 7.

9. The composition according to claim 8, characterized in that it contains peptide No. 3 (4B) and peptide No. 1 (2B).

10. A composition, characterized in that it contains one or several synthetic peptides of the formula (I) according to claim 1, and one or more recombinant peptides of HIV-l of the group OR.

11. A composition, characterized in that one or several synthetic peptides of the formula (I), according to claim 1, and one or more synthetic or recombinant HIV-1 and / or HIV-2 peptides.

12. An immunodification process characterized in that it puts into operation one or several synthetic peptides of the formula (I), according to any of claims 1 to 7.

13. An immunosodification process characterized in that it puts into operation a composition according to any of claims 8 to 11.

14. A diagnostic kit, characterized in that it includes at least one synthetic peptide of the formula (I), according to any one of claims 1 to 7, or a composition according to any of claims 8 to 11.