Design and study of peptide-based inhibitors of amylin cytotoxicity.
The incidence of type II diabetes is on the increase each year and the World Health Organisation (WHO) predicts there to be over 360 million diabetic patients worldwide by the year 2030. Deposits consisting mainly of a small protein, called islet amyloid polypeptide (amylin), which aggregates into oligo-/polymeric beta sheet structures is responsible for cytotoxicity to the pancreatic beta-cells, thus inhibition of this process has been explored as a potential prevention or treatment. N-Methylated and non N-methylated peptides spanning the length of amylin(1-37) were synthesised and evaluated for their inhibition of full length amylin mediated cytotoxicity to RIN-5F cells. The non N-methylated peptides were very effective in inhibiting the cytotoxicity while the N-methylated peptides were not. Both the N-methylated and non N-methylated versions of the 29-34 region were equally effective.
Muthusamy
Karen
K
Department of Biochemistry, University of KwaZulu Natal, South Africa.
Arvidsson
Per I
PI
Govender
Patrick
P
Kruger
Hendrik G
HG
Maguire
Glenn E M
GE
Govender
Thavendran
T
D000595:Amino Acid Sequence; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000235:genetics; D002942:Circular Dichroism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D058228:Islet Amyloid Polypeptide; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000235:genetics / Q000494:pharmacology*
D000682:Amyloid; D007004:Hypoglycemic Agents; D058228:Islet Amyloid Polypeptide; D010455:Peptides