Structure-Activity Based Study of the Smac-Binding Pocket Within the DIR3 Domain of XIAP

Journal Article · Mon Jan 01 04:00:00 EST 2007 · BioOrganic and Medicinal Chemistry Letters

OSTI ID:930397

Wist, A; Gu, L; Riedl, S; Shi, Y; McLendon, G

A small series of peptide mimics was designed and synthesized to contain a heterocyclic ring in place of the potentially labile N-terminal peptide bond of the tetrapeptide containing the Smac-XIAP-binding motif. Two Smac mimics were shown to bind to the BIR3 domain of XIAP with moderate affinity and one displayed increased activity in cells relative to the Smac peptides. The structures of BIR3-XIAP in complex with a Smac peptide and a peptide mimic were solved and analyzed to elucidate the structure-activity relationship surrounding the Smac-binding domain within BIR3-XIAP.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 930397
• Report Number(s): BNL--81123-2008-JA
• Journal Information: BioOrganic and Medicinal Chemistry Letters, Journal Name: BioOrganic and Medicinal Chemistry Letters Vol. 15; ISSN 0960-894X
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
AFFINITY
APOPTOSIS
CRYSTAL STRUCTURE
INHIBITION
PEPTIDES
PROTEINS
STRUCTURE-ACTIVITY RELATIONSHIPS
national synchrotron light source