Synthesis and conformational analysis of the insulin-like 4 gene product

Insulin-like 4 (INSL-4) is a protein expressed in the early placenta. its p rimary structure is insulin-like with reference to the distribution of cyst eine residues and the single chain proform. Insulin-like 4 was generated by solid-phase peptide synthesis of the two chains followed by the sequential synthesis of the three disulfide bonds. Two disulfide isomers were produce d, one with an insulin-like disulfide bonding pattern and the other with a reversed chain orientation. The CD spectra of the two disulfide isomers wer e indistinguishable without any features produced by periodic structures. I n addition, the hydrodynamic properties of the two isomers were identical w hich implied a very open structure of the disulfide-bonded two-chain molecu les. It appears that insulin-likeness cannot be defined solely on the basis of the primary structure of cDNA.