Peptide-biphenyl hybrids as calpain inhibitors.
Calpain is a cysteine protease that is activated by Ca2+. The over-activation of calpain, which occurs on increasing Ca2+ concentration, causes a variety of diseases. This paper reports experimental results on the inhibition of calpain I (mu-calpain) by peptide-biphenyl hybrids. We have found that some peptide-biphenyl hybrids, with aromatic amino acids in the peptide chains, inhibit calpain with IC50 values in the nanomolar range. Since the peptide-biphenyl hybrids reported in the present paper do not possess a reactive electrophilic functionality, we hypothesize that they interfere with the activation of calpain by Ca2+, and present experimental and computational results on the binding of peptide-biphenyl hybrids to Ca2+.
Montero
Ana
A
Instituto de Química Orgánica General, C.S.I.C., Juan de la Cierva 3, E-28006 Madrid.
Mann
Enrique
E
Chana
Antonio
A
Herradón
Bernardo
B
D001713:Biphenyl Compounds / Q000032:analysis / Q000737:chemistry*; D006023:Glycoproteins / Q000032:analysis / Q000737:chemistry*; D010455:Peptides / Q000032:analysis / Q000737:chemistry*
D001713:Biphenyl Compounds; D006023:Glycoproteins; D010455:Peptides; C039304:calpain inhibitors