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Biophysical insight into the heparin‐peptide interaction and its modulation by a small molecule
Author(s) -
Tiwari Neha,
Srivastava Ankit,
Kundu Bishwajit,
Munde Manoj
Publication year - 2018
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.2674
Subject(s) - heparin , peptide , modulation (music) , chemistry , biophysics , small molecule , molecule , biochemistry , biology , organic chemistry , physics , acoustics
The heparin‐protein interaction plays a vital role in numerous physiological and pathological processes. Not only is the binding mechanism of these interactions poorly understood, studies concerning their therapeutic targeting are also limited. Here, we have studied the interaction of the heparin interacting peptide (HIP) from Tat (which plays important role in HIV infections) with heparin. Isothermal titration calorimetry binding exhibits distinct biphasic isotherm with two different affinities in the HIP‐heparin complex formation. Overall, the binding was mainly driven by the nonionic interactions with a small contribution from ionic interactions. The stoichiometric analysis suggested that the minimal site for a single HIP molecule is a chain of 4 to 5 saccharide molecules, also supported by docking studies. The investigation was also focused on exploiting the possibility of using a small molecule as an inhibitor of the HIP‐heparin complex. Quinacrine, because of its ability to mimic the HIP interactions with heparin, was shown to successfully modulate the HIP‐heparin interactions. This result demonstrates the feasibility of inhibiting the disease relevant heparin‐protein interactions by a small molecule, which could be an effective strategy for the development of future therapeutic agents.