[Efficient synthesis of natural alpha-conotoxins and their analogs].
An efficient scheme for the synthesis of alpha-conotoxins, containing 12-18 amino acid residues and two disulfide bridges, was proposed. Its advantages are: (1) the avoidance of orthogonal protections of Cys residues; (2) a lower number of stages in a cycle of the peptide chain elongation by the method of solid phase synthesis; (3) the linear product is sufficiently pure for being used at the next stage of the disulfide bond formation without additional purification; and (4) a substantially reduced time of oxidation to disulfides at pH 10, which led to the target product in a high yield. A number of natural alpha-conotoxins (GI, ImI, EI, MII, and SIA), affecting the muscle and neuronal nicotinic acetylcholine receptors of various types, and several new analogues of these conotoxins (in particular, [Tyr10]ImI, [Gln12]GI, and [Ser1]GI) were synthesized by this scheme. They were used for elucidating the spatial structure of alpha-conotoxins by 1H NMR spectroscopy and for studying the ligand-binding sites of their receptors.
Zhmak
M N
MN
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, GSP Moscow, 117997 Russia. zhmak@ibch.ru
Kasheverov
I E
IE
Utkin
Iu N
IuN
Tsetlin
V I
VI
Vol'pina
O M
OM
Ivanov
V T
VT
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D020916:Conotoxins / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction
D020916:Conotoxins; C029960:conotoxin GI