. 63, 3089 (1985). Reaction conditions for the synthesis of thioarnide, arnidoxirne, and N-substituted arnidine analogs of the peptide bond are described. Several new arnidine analogs of the chernotactic peptide f-Met-Leu-Phe-OR were synthesized using the thioarnides as precursors. ' The assignment of the E / Z configuration was accomplished by nuclear magnetic resonance. The biological activity of these analogs is briefly described.GILLES SAUVE, VANCA S. RAO, GILLES LAJOIE et BERNARD BELLEAU. Can. J. Chern. 63, 3089 (1985). Des conditions de reaction pour la synthitse de thioarnides, d'arnidoxirnes et d'arnidines N-substitukes analogues au lien peptidique sont dkcrites. Plusieurs analogues du peptide chirniotactique f-Met-Leu-Phe-OR contenant une fonction arnidine N-substituke furent synthCtisks i partir de prkcurseurs thioarnides. L'attribution de la configuration E et Z est faite par analyse spectroscopique de rksonance rnagnetique nucleaire. L'activitC biologique de ces analogues est decrite briivernent.

No abstract

Indolicidin, a novel tryptophan‐rich microbicidal tridecapeptide amide isolated originally from granules of bovine neutrophils, has been prepared by optimized manual and automated protocols of stepwise solid‐phase synthesis with Nα‐9‐fluorenylmethyloxycarbonyl (Fmoc) amino acid derivatives. Both standard polystyrene (PS) and polyethylene glycol‐polystyrene (PEG‐PS) graft supports were used in combination with handles that provide C‐terminal peptide amides: 5‐(4‐Fmoc‐aminomethyl‐3,5‐dimethoxyphenoxy)valeric acid (PAL) or 5‐(9‐Fmoc‐aminoxanthen‐2‐oxy)valeric acid (XAL). Final deprotection/cleavage was carried out with reagent K, trifluoroacetic acid–phenol–water–thioanisole–1,2‐ethanedithiol (82.5:5:5:5:2.5), or reagent B, trifluoroacetic acid–phenol–water–tri(isopropyl)silane (88:5:5:2), and related cocktails. Initial purities as high as 93% were obtained immediately following cleavage. In the largest‐scale synthesis carried out, 0.8 g of HPLC‐purified indolicidin (> 99% pure) was obtained, representing a 39% overall yield based on C‐terminal Arg(Pmc) anchored to PAL‐PS‐resin. The main synthetic product, and some by‐products, were characterized by analytical high‐performance liquid chromatography (HPLC), sequencing, and fast atom bombardment mass spectrometry (FABMS). The antimicrobial potencies of natural and synthetic indolicidin, as determined by in vitro antibacterial and antifungal assays, were identical. Further, the reactivities of natural and synthetic peptides with anti‐indolicidin antibody were indistinguishable. © Munksgaard 1995.

Mono-and dipeptide derivatives of C4-/?-aminoalkyl carbapenems were synthesized by the use of amino acid TV-carboxy anhydride for the peptide bond formation. They were shown to act as prodrugs in vivo while imparting the much desired chemical stability. The /?-chloroalanyl derivative was suggested to act, in part, as a "dual-purpose" antibacterial.