Biosynthetic engineered B28K–B29P human insulin monomer structure in water and in water/acetonitrile solutions
- 323 Downloads
Insulin engineering is a process intended to obtain desired therapeutic properties by rationally designed sequence mutations of a wild type insulin (HI) which originally consists of two chains, having 21 and 30 amino acids (AA) in chain A and B, respectively, held together by two disulfide bridges, namely A7C–B7C and A20C–B19C and intra strand bridge in chain A; A6C–A11C. It is known that human insulin (HI) circulates in the bloodstream as a monomer and in such a form passes effectively through the capillary membrane and binds to the insulin receptor (DeFelippis et al. 2001). An increase in insulin concentration causes formation of noncovalent dimers and higher oligomers. These entities are present in pharmaceutical preparations. Natural propensity of insulin to self-association has meaningful implication on pharmacokinetic behaviour upon hormone administration. Insulin diffusion into tissues entails progressive dissociation of hexamers into dimers and monomers....
KeywordsTertiary Structure Human Insulin Insulin Lispro Insulin Detemir Dime Interface
This research was conducted mainly within the frame of a Key Research Project under contract No. POIG 01.01.01-14—007/08-00. Part of these results was a research project supported from Ministry of Science and Higher Education funds reserved for science during a period of 2009–2012.
- Borowicz P, Płucienniczak A, Mikołajczyk J, Głąbski T, Kurzynoga D, Mikiewicz-Syguła D, Wojtowicz-Krawiec A, Zieliński M, Kęsik-Brodacka M, Adamczewska-Cecuda V et al (2009) Institute of Biotechnology and Antibiotics assignee. Novel insulin analogues of prolonged activity. Patent WO 2010/002283. PolandGoogle Scholar
- Borowicz P, Bocian W, Sitkowski J, Bednarek E, Mikiewicz-Syguła D, Błażej-Sosnowska S, Bogiel M, Rusek D, Kurzynoga D, Kozerski L (2011) Novel recombinant insulin analogue with flexible C-terminus in B chain. NMR structure of biosynthetic engineered A22G–B31K-B32R human insulin monomer in water/acetonitrile solution. Int J Biol Macromol 49(4):548–554CrossRefGoogle Scholar
- Lepore M, Pampanelli S, Fanelli C, Porcellati F, Bartocci L, Di Vincenzo A, Cordoni C, Costa E, Brunetti P, Bolli GB (2000) Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes 49(12):2142–2148CrossRefGoogle Scholar