Asymmetric synthesis of Boc-N-methyl-p-benzoyl-phenylalanine. Preparation of a photoreactive antagonist of substance P.
The asymmetric synthesis of (S)-Boc-N-methyl-p-benzoyl-phenylalanine was performed by alkylation of sultam Boc-sarcosinate. The levorotatory sultam led to (S)-Boc-N-methyl amino acids with high optical purity. This photoreactive amino acid was incorporated into the sequence of a Substance P peptide antagonist. Comparison of the affinity and antagonistic properties of Biotinyl-apa-[D-Pro9, MePhe(pBz)10, Trp11]SP for human tachykinin NK-1 receptor demonstrated that this photoreactive antagonist should be a suitable tool for photolabelling studies.
Karoyan
P
P
Laboratoire de Chimie Organique Biologique associé au CNRS, Université P. et M. Curie, UMR 7613, Paris, France.
Sagan
S
S
Clodic
G
G
Lavielle
S
S
Chassaing
G
G
D000478:Alkylation; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D064729:Neurokinin-1 Receptor Antagonists; D010649:Phenylalanine / Q000138:chemical synthesis*; D010777:Photochemistry; D018041:Receptors, Neurokinin-2 / Q000378:metabolism; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C117558:N-(tert-butoxycarbonyl)-N-methyl-4-benzoylphenylalanine; D064729:Neurokinin-1 Receptor Antagonists; D018041:Receptors, Neurokinin-2; C117612:substance P, biotinyl-apa-Pro(9)-MePhe(pBz)(10)-Trp(11)-; D013373:Substance P; D010649:Phenylalanine; D001710:Biotin; D000242:Cyclic AMP