title: Secretin self-assembles and interacts spontaneously with phospholipids in vitro.
abstract: Secretin, a 27-amino acid neuropeptide, is a member of the secretin/glucagon/vasoactive intestinal polypeptide (VIP) superfamily of amphipathic peptides. The peptide modulates gastrointestinal and neuronal function and is currently being evaluated for the treatment of autism. However, as most peptides, it has a short circulation half-life. Previously, we have shown that VIP self-assembles in aqueous environment and interacts with a biomimetic phospholipid membrane. These in vitro characteristics increase VIP half-life and bioactivity in vivo. The purpose of this study was to investigate whether secretin exhibits similar properties in vitro by forming micelles in aqueous solution and interacting with phospholipids. Results of this study demonstrated that secretin self-assembles to form micelles in HEPES buffer at 25 degrees C above approximately 0.4 microM. Additionally, secretin interacts with a biomimetic phospholipid membrane as indicated from a significant increase in membrane surface pressure (from 25.5 +/- 1.3 to 32.5 +/- 3.0, P < 0.05). Importantly, the peptide undergoes conformational transition from predominantly random coil in saline to alpha-helix in the presence of phospholipid, distearoyl-phosphatidylcholine-poly(ethylene) glycol (mol mass 2000) micelles. We suggest that these distinct biophysical attributes could modulate secretin bioactivity in vivo.
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, 60612, USA.
authors.forename: Salil
authors.initials: S
authors.lastname: Gandhi
authors.forename: Israel
authors.initials: I
authors.lastname: Rubinstein
authors.forename: Takaya
authors.initials: T
authors.lastname: Tsueshita
authors.forename: Hayat
authors.initials: H
authors.lastname: Onyuksel
mesh_terms: D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008823:Micelles; D010455:Peptides / Q000737:chemistry; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012633:Secretin / Q000737:chemistry* / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors
chemical_list: D008823:Micelles; D010455:Peptides; D010743:Phospholipids; D012633:Secretin