Design and synthesis of type-III mimetics of ShK toxin

Author(s): Baell, JB; Harvey, AJ; Norton, RS;
Details: Publication Year 2002-04,Volume 16,Issue #4,Page 245-262
Journal Title: JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
Publication Type: Journal Article
Abstract: ShK toxin is a structurally defined, 35-residue polypeptide which blocks the voltage-gated Kv1.3 potassium channel in T-lymphocytes and has been identified as a possible immunosuppressant. Our interest lies in the rational design and synthesis of type-III mimetics of protein and polypeptide structure and function. ShK toxin is a challenging target for mimetic design as its binding epitope consists of relatively weakly binding residues, some of which are discontinuous. We discuss here our investigations into the design and synthesis of 1st generation, small molecule mimetics of ShK toxin and highlight any principles relevant to the generic design of type-III mimetics of continuous and discontinuous binding epitopes. We complement our approach with attempted pharmacophore-based database mining.
Publisher: KLUWER ACADEMIC PUBL
Keywords: POTASSIUM CHANNELS; SEA-ANEMONE; T-LYMPHOCYTES; K+ CHANNELS; BINDING; INHIBITOR; MUTATION
Publisher's Version: https://doi.org/10.1023/A:1016310602813
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2002-04-01 12:00:00