Solid-phase combinatorial synthesis of peptide-biphenyl hybrids as calpain inhibitors.
[structure: see text] The combinatorial parallel synthesis of peptide-biphenyl hybrids on solid support using state of the art of peptide synthesis is reported. Key steps were the N to C addition of an amino moiety, hydrolysis of the methyl ester, and the absence of cross-linked compounds when the 2,2'-diamino-1,1'-biphenyl was incorporated. When tested for activity as calpain inhibitors, some of the compounds exhibited IC(50) values in the nanomolar range.
Montero
Ana
A
Instituto de Química Orgánica General, C.S.I.C., Juan de la Cierva 3, 28006-Madrid, Spain.
Albericio
Fernando
F
Royo
Miriam
M
Herradón
Bernardo
B
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002154:Calpain / Q000037:antagonists & inhibitors*; D004952:Esters / Q000737:chemistry; D006868:Hydrolysis; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology
D000596:Amino Acids; D001713:Biphenyl Compounds; D004952:Esters; D010455:Peptides; D011480:Protease Inhibitors; D002154:Calpain