Per Hertz Hansen

Assembly of high-affinity insulin receptor agonists and antagonists from peptide building blocks

Insulin is thought to elicit its effects by crosslinking the two extracellular α-subunits of its receptor, thereby inducing a conformational change in the receptor, which activates the intracellular tyrosine kinase signaling cascade. Previously we identified a series of peptides binding to two discrete hotspots on the insulin receptor. Here we show that covalent linkage of such peptides into homodimers or heterodimers results in insulin agonists or antagonists, depending on how the peptides are linked. An optimized agonist has been shown, both in vitro and in vivo, to have a potency close to that of insulin itself. The ability to construct such peptide derivatives may offer a path for developing agonists or antagonists for treatment of a wide variety of diseases.

Novel avidin and streptavidin binding sequences found in synthetic peptide libraries

Synthetic resin‐bound peptide libraries made of protein l‐amino acids have been synthesized. During screening of the libraries, peptides that bind to avidin have been identified containing a novel motif with two histidines separated by one residue. A sub‐library was synthesized and screened, and new critical residues appeared surrounding the two histidines. Additionally peptide libraries made of d‐amino acids have been screened with avidin and streptavidin and novel motifs have been found.

Primary structure of fox (Vulpes vulpes) proinsulin based on sequence studies of pancreatic peptides and cDNA

Insulin and C‐peptide were extracted and purified from fox (Vulpes vulpes) pancreas using gel filtration, ion‐exchange chromatography and HPLC. Chromatographic data for the insulin, as well as for its oxidized and carboxymethylated chains proved it to be identical to that of polar fox (Alopex lagopus) and dog. The sequence analysis of a peptide which was assumed to be the corresponding C‐peptide revealed that it comprises 23 amino acid residues and is identical to the C‐peptide fragment isolated from dog pancreas; it differs from polar fox C‐peptide by a single substitution (Asp→Glu). mRNA was isolated from pancreatic tissue and cDNA was obtained by reverse transcription. A polymerase chain reaction was performed using gene‐specific primers to obtain a DNA fragment corresponding to part of fox proinsulin. DNA sequencing revealed 100% identity to dog proinsulin at the protein level, although some amino acids were encoded by different codons. The total sequence of proinsulin was deduced from these results. Copyright