Solid Phase Synthesis of an Analogue of Insulin, A0:R glargine, That Exhibits Decreased Mitogenic Activity
Seon-Yeong Kwak, Briony E Forbes, Yoon-Sik Lee, Alessia Belgi, John D Wade, Mohammed Akhter Hossain
INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS | SPRINGER | Published : 2010
Numerous analogues of insulin have been prepared over the past three decades for use in diabetic therapy. However, only two long-acting insulins have been approved for clinical use. One is Levemir (Novo Nordisk) and the other is Lantus (Sanofi-Aventis). Glargine (commercial name: Lantus) is characterized by a substitution of Gly in place of Asn at the C terminus of the A-chain and addition of two Arg residues to the C terminus of the B-chain. Despite the clinical advantages of glargine, it is not without concern that its increased affinity for the IGF-1 receptor may correlate with increased mitogenic activity. Recently, a systematic study of modified analogues of glargine showed that placeme..View full abstract
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Awarded by National Health and Medical Research Council (NHMRC) of Australia
This study was funded by a grant to JDW from the National Health and Medical Research Council (NHMRC) of Australia (ID no. 508995). JDW is a recipient of a Research Fellowship from the NHMRC, BEF is a recipient of a University of Adelaide Biochemistry Fellowship, while MAH is the recipient of a John T Reid Charitable Trusts Fellowship. Seon-Yeong was the recipient of a travel award from the Brain Korea 21 Program to the Howard Florey Institute, Melbourne, Australia. We would like to thank Ms Linda Chan for amino acid analysis and Ms Kerrie McNeil with assistance with the receptor binding and DNA synthesis assays.