title: Reversible Insulin Hexamer Assembly Promoted by Ethyl Violet: pH-Controlled Uptake and Release.
abstract: Therapeutically improved long-acting insulin preparations require in-depth understanding of the hexamer assembly, structural selectivity, and its stability in solution. This Letter demonstrates, for the first time, an efficient method for the hexamerization of human insulin by a structure-specific triphenylmethane (TPM) dye, Ethyl Violet (EV), particularly, in the absence of Zn2+. Upon detailed spectroscopic evaluation and comparison with other TPM homologues, we establish that the diethylamino phenyl arms of EV are specific and effective in clipping the three dimer helices in a hexameric assembly. We establish that at physiological pH 7.4 and in the presence of the EV, insulin exists predominantly in its hexameric form, a condition appropriate for storage and preparation of long-acting insulin formulations. On the other hand, the disassembly of the hexamer into the monomeric form is accomplished at pH 5, highlighting its potential as a delivery vehicle for such custom-modified dyes/drugs.
authors.affiliation: Radiation & Photochemistry Division, Bhabha Atomic Research Centre , Mumbai 400 085, India.|Homi Bhabha National Institute , Training School Complex, Anushaktinagar, Mumbai 400 094, India.
authors.forename: Jyotirmayee
authors.initials: J
authors.lastname: Mohanty
authors.affiliation: Radiation & Photochemistry Division, Bhabha Atomic Research Centre , Mumbai 400 085, India.|Student, BARC-SPPU PhD Program, Department of Chemistry, Savitribai Phule Pune University , Pune 411 007, India.
authors.forename: Meenakshi N
authors.initials: MN
authors.lastname: Shinde
authors.affiliation: Radiation & Photochemistry Division, Bhabha Atomic Research Centre , Mumbai 400 085, India.
authors.forename: Nilotpal
authors.initials: N
authors.lastname: Barooah
authors.affiliation: Radiation & Photochemistry Division, Bhabha Atomic Research Centre , Mumbai 400 085, India.|Homi Bhabha National Institute , Training School Complex, Anushaktinagar, Mumbai 400 094, India.
authors.forename: Achikanath C
authors.initials: AC
authors.lastname: Bhasikuttan