Na[(tert-Butoxy)carbonyl]-2-diazo-~-histidine methyl ester 1 was synthesized starting from the corresponding L-histidine derivative. The physico-chemical properties of this new photoactivatable amino-acid derivative were established. The synthetic precursor of 1,2-amino-~-histidine derivative 3, was best isolated and characterized as 2-amino-Nr-[(tert-butoxy)carbonyl]-~T-tosyl-~-histidine methyl ester (4). Selective deprotections of 4 (N"-Boc, N'-Tos, COOMe) were achieved, thus allowing the use of the corresponding products in peptide synthesis. The optically active dipeptides 8 and 9 were synthesized by coupling 2-amino-Nr-tosyl-~-histidine methyl ester ( 5 ) with N-[(tert-butoxy)cdrbonyl]-L-alanine and N'-[(rert-buto~y)carbonyl]-N~-tosyl-~-histidine (6) with L-alanine methyl ester, respectively. The question of selective diazotization of a 2-aminohistidine residue in a synthetic peptide was studied using competitive diazotizations between 2-amino-lH-imidazole and several amino-acid derivatives susceptible to undergo nitrosylation. The results show that synthetic photoactivatable peptides incorporating a 2-diazohistidine residue might become useful photoaffinity probes.Introduction. -The discovery of numerous peptides involved in the recognition and modulation of hormone or neuromediator receptors stimulated the design and the synthesis of peptide analogs in order to study ligand-receptor interactions. Among these probes, photoactivatable structures were conceived to label irreversibly the receptor at a target binding site by means of photoaffinity labelling experiments [l]. Two major results are expected from this approach, either to identify and characterize an unknown receptor or to define at a molecular level the ligand-receptor interactions.The synthesis of photoactivatable peptides was first conceived by tagging a photosensitive group to an existing peptide. Most of the described examples used electrophilic reagents bearing an arylazido or a benzophenone moiety, the coupling of the reagent to the peptide being generally directed towards the C-terminal [2] or towards nucleophilic residues existing on the peptide such as the primary amino group of a lysine side chain [3]. Besides the problem of selectivity of modification which can arise, the major limitation of this method is the consequent structural changes caused by the attachment of the photosensitive group on the natural ligand which often induces a loss in binding affinity. The design of a photosensitive amino-acid analog structurally related to a natural amino acid and which could be incorporated in the peptide during the synthesis (solid phase or in solution), would overcome the above mentioned limitations. As such, the 4'-azidophenylalanine derivative [4] has been developed and used as a substitute for phenylalanine in several peptides [5]. The syntheses of those peptides used a 4'-nitrophenylalanine precursor which was subsequently transformed to the corresponding 4'-azido derivative.

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A strategy for the introduction of a photoactivatable amino acid, e.g. the 2‐diazohistidine derivative (IV), into a peptide is developed using the 2‐aminohistidine derivative (VII) for the synthesis of peptides such as (IX) and (XI).