Collagenolytic Matrix Metalloproteinase Activities toward Peptomeric Triple-Helical Substrates

Although collagenolytic matrix metalloproteinases (MMPs) possess common domain organizations, there are subtle differences in their processing of collagenous triple-helical substrates. In this study, we have incorporated peptoid residues into collagen model triple-helical peptides and examined MMP activities toward these peptomeric chimeras. Several different peptoid residues were incorporated into triple-helical substrates at subsites P3, P1, P1′, and P10′ individually or in combination, and the effects of the peptoid residues were evaluated on the activities of full-length MMP-1, MMP-8, MMP-13, and MMP-14/MT1-MMP. Most peptomers showed little discrimination between MMPs. However, a peptomer containing N-methyl Gly (sarcosine) in the P1′ subsite and N-isobutyl Gly (NLeu) in the P10′ subsite was hydrolyzed efficiently only by MMP-13 [nomenclature relative to the α1(I)772–786 sequence]. Cleavage site analysis showed hydrolysis at the Gly–Gln bond, indicating a shifted binding of the triple helix compared t...