title: Comparative analysis of the substrate preferences of two post-proline cleaving endopeptidases, prolyl oligopeptidase and fibroblast activation protein α.
abstract: Post-proline cleaving peptidases are promising therapeutic targets for neurodegenerative diseases, psychiatric conditions, metabolic disorders, and many cancers. Prolyl oligopeptidase (POP; E.C. 3.4.21.26) and fibroblast activation protein α (FAP; E.C. 3.4.24.B28) are two post-proline cleaving endopeptidases with very similar substrate specificities. Both enzymes are implicated in numerous human diseases, but their study is impeded by the lack of specific substrate probes. We interrogated a combinatorial library of proteolytic substrates and identified novel and selective substrates of POP and FAP. These new sequences will be useful as probes for fundamental biochemical study, scaffolds for inhibitor design, and triggers for controlled drug delivery.
authors: Biosciences Division, SRI International, Harrisonburg, VA 22802, USA.
authors: Kalyani
authors: K
authors: Jambunathan
authors: Douglas S
authors: DS
authors: Watson
authors: Aaron N
authors: AN
authors: Endsley
authors: Krishna
authors: K
authors: Kodukula
authors: Amit K
authors: AK
authors: Galande
mesh_terms: D020816:Amino Acid Motifs; D000596:Amino Acids / Q000737:chemistry; D001671:Biochemistry / Q000379:methods; D020650:Combinatorial Chemistry Techniques; D016503:Drug Delivery Systems; D010450:Endopeptidases; D005456:Fluorescent Dyes / Q000737:chemistry; D018093:Gelatinases / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry*; D019151:Peptide Library; D011392:Proline / Q000737:chemistry; D000085822:Prolyl Oligopeptidases; D011994:Recombinant Proteins / Q000737:chemistry; D012697:Serine Endopeptidases / Q000737:chemistry*; D013379:Substrate Specificity; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000596:Amino Acids; D010450:Endopeptidases; D005456:Fluorescent Dyes; D018093:Gelatinases; D008565:Membrane Proteins; D019151:Peptide Library; D011392:Proline; D000085822:Prolyl Oligopeptidases; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C000705287:PREPL protein, human