Modifications of the human urocortin 2 peptide that improve pharmacological properties.

Recently, we demonstrated that the corticotropin releasing factor 2 receptor agonist, urocortin 2, demonstrated anti-atrophy effects in rodent skeletal muscle atrophy models. Compared to other CRF2R agonists however, the in vivo pharmacological potency of urocortin 2 is poor when it is administered by continuous subcutaneous infusion. Therefore, we attempted to modify the structure of urocortin 2 to improve in vivo efficacy when administered by subcutaneous infusion.

Sauvagine analogs selective for corticotropin releasing factor 2 receptor: effect of substitutions at positions 35 and 39 on CRF2R selectivity.

Corticotropin releasing factor 2 receptor selective analogs of the amphibian peptide sauvagine, a member of the corticotropin releasing factor (CRF) peptide family, have therapeutic potential for the treatment of skeletal muscle atrophy. Previously, we demonstrated that [P11X12X13]Svg peptides have improved CRF2R selectivity, although not to the level of CRF2R selective hormones such as urocortin 2 and urocortin 3. Since we also demonstrated a potential for improvement in selectivity of sauvagine by modifications of residues 35 and 39, we investigated substitutions of these amino acids in selected [P11X12X13]Svg peptides.

Discovery of corticotropin releasing factor 2 receptor selective sauvagine analogues for treatment of skeletal muscle atrophy.

The corticotropin release factor 2 receptor (CRF2R) has many biological activities including modulation of the stress response. Recently, we have demonstrated that CRF2R activation functions to prevent skeletal muscle wasting resulting from a variety of physiological stimuli. Thus we are interested in identifying CRF2R selective agonists with optimal pharmacological properties for use in treating muscle wasting diseases.

Determinants of corticotropin releasing factor. Receptor selectivity of corticotropin releasing factor related peptides.

The corticotropin-releasing factor (CRF) peptide family is an important target in pharmaceutical research. The CRF system consists of two receptors, corticotropin releasing factor receptor 1 (CRF1R) and corticotropin releasing factor receptor 2 (CRF2R), a nonreceptor binding protein, and the peptide agonists of these receptors. The recent discovery of the CRF2R selective peptide agonists, UCN2, UCN3 and URP, prompted investigations into the structural source of CRF1R versus CRF2R selectivity of CRF peptide family members.