Conformationally restricted formyl methionyl tripeptide chemoattractants: a three-dimensional structure-activity study of analogs incorporating a C alpha,alpha-dialkylated glycine at position 2.
The conformationally restricted CHO-L-Met-Xxx-L-Phe-OY (where Xxx = Aib, Ac3c, Ac5c, Ac6c, and Ac7c; Y = H, Me) tripeptides, analogs of the chemoattractant CHO-L-Met-L-Leu-L-Phe-OH, have been synthesized in solution by classical methods and fully characterized. Compounds were compared to determine the combined effect of backbone conformational preferences and side-chain bulkiness on the relation of three-dimensional structure to biological activity. Each peptide was tested for its ability to induce granule enzyme secretion from rabbit peritoneal polymorphonuclear leukocytes. In parallel, a conformational analysis on the CHO-blocked peptide and their tertbutyloxycarbonylated synthetic precursors was performed in the crystal state and in solution using X-ray diffraction, infrared absorption, and 1H nuclear magnetic resonance. The biological and conformational data are discussed in relation to the proposed model of the chemotactic peptide receptor of rabbit neutrophils.
Toniolo
C
C
University of Padova.
Crisma
M
M
Valle
G
G
Bonora
G M
GM
Polinelli
S
S
Becker
E L
EL
Freer
R J
RJ
Sudhanand
Rao
R B
RB
Balaram
P
P
D000478:Alkylation; D000595:Amino Acid Sequence; D000818:Animals; D005998:Glycine; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D011817:Rabbits; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D009842:Oligopeptides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005998:Glycine