Hemopressin Forms Self-Assembled Fibrillar Nanostructures under Physiologically Relevant Conditions

• Published in: Biomacromolecules Vol. 13; no. 3; pp. 579 - 583
• Main Authors: Bomar, Martha G, Samuelsson, Steven J, Kibler, Patrick, Kodukula, Krishna, Galande, Amit K
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 12.03.2012
• Subjects: Aminoacids, peptides. Hormones. Neuropeptides; Analytical, structural and metabolic biochemistry; Animals; Applied sciences; Biological and medical sciences; Circular Dichroism; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Hemoglobins - chemistry; Hemoglobins - metabolism; Hydrogen-Ion Concentration; Microscopy, Electron, Transmission; Models, Molecular; Nanostructures; Natural polymers; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Physicochemistry of polymers; Proteins; Rats; Receptor, Cannabinoid, CB1 - agonists; Structure-Activity Relationship; Self assembly; Circular dichroism spectrum; Nonapeptide; Nanostructure; Aqueous solution; Fibrillar structure; Experimental study; Conformation
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm201836f

The nonapeptide hemopressin, which is derived from the α chain of hemoglobin, has been reported to exhibit inverse agonist activity against the CB1 receptor. Administration of this peptide in animal models led to decreased food intake and elicited hypotensive and antinociceptive effects. On the basis of hemopressin’s potential in therapeutic applications and the lack of a structure–activity relationship study in literature, we aimed to determine the conformational features of hemopressin under physiological conditions. We conducted transmission electron microscopy experiments of hemopressin, revealing that it self-assembles into fibrils under aqueous conditions at pH 7.4. Circular dichroism and nuclear magnetic resonance experiments indicate that the peptide adopts a mostly extended β-like structure, which may contribute to its self-assembly and fibril formation.