title: Peptide truncation leads to a twist and an unusual increase in affinity for casitas B-lineage lymphoma tyrosine kinase binding domain.
abstract: We describe truncation and SAR studies to identify a pentapeptide that binds Cbl tyrosine kinase binding domain with a higher affinity than the parental peptide. The pentapeptide has an alternative binding mode that allows occupancy of a previously uncharacterized groove. A peptide library was used to map the binding site and define the interface landscape. Our results suggest that the pentapeptide is an ideal starting point for the development of inhibitors against Cbl driven diseases.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68022, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Kumar
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Yuan
authors.forename: Nicholas Y
authors.initials: NY
authors.lastname: Palermo
authors.forename: Lin
authors.initials: L
authors.lastname: Dong
authors.forename: Gulzar
authors.initials: G
authors.lastname: Ahmad
authors.forename: G L
authors.initials: GL
authors.lastname: Lokesh
authors.forename: Carol
authors.initials: C
authors.lastname: Kolar
authors.forename: Smitha
authors.initials: S
authors.lastname: Kizhake
authors.forename: Gloria E O
authors.initials: GE
authors.lastname: Borgstahl
authors.forename: Hamid
authors.initials: H
authors.lastname: Band
authors.forename: Amarnath
authors.initials: A
authors.lastname: Natarajan
mesh_terms: D001665:Binding Sites; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D050722:Oncogene Protein v-cbl / Q000737:chemistry* / Q000378:metabolism; D019151:Peptide Library; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D009842:Oligopeptides; D050722:Oncogene Protein v-cbl; D019151:Peptide Library; D011505:Protein-Tyrosine Kinases