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Exploring the Conformational Space of Growth-Hormone-Releasing Hormone Analogues Using Dopant Assisted Trapped Ion Mobility Spectrometry-Mass Spectrometry.

08:00 EDT 12th July 2019 | BioPortfolio

Summary of "Exploring the Conformational Space of Growth-Hormone-Releasing Hormone Analogues Using Dopant Assisted Trapped Ion Mobility Spectrometry-Mass Spectrometry."

Recently, we proposed a high-throughput screening workflow for the elucidation of agonistic or antagonistic growth hormone-releasing hormone (GHRH) potencies based on structural motif descriptors as a function of the starting solution. In the present work, we revisited the influence of solution and gas-phase GHRH molecular microenvironment using trapped ion mobility-mass spectrometry (TIMS-MS). The effect of the starting solvent composition (10 mM ammonium acetate (NHAc), 50% methanol (MeOH), 50% acetonitrile (MeCN), and 50% acetone (Ac)) and gas-phase modifiers (N, N + MeOH, N + MeCN, and N + Ac) on the conformational states of three GHRH analogues, GHRH (1-29), MR-406, and MIA-602, is described as a function of the trapping time (100-500 ms). Changes in the mobility profiles were observed showing the dependence of the conformational states of GHRH analogues according to the molecular microenvironment in solution, suggesting the presence of solution memory effects on the gas-phase observed structures. Modifying the bath gas composition resulted in smaller mobilities that are correlated with the size and mass of the organic modifier, and more importantly led to substantial changes in relative abundances of the IMS profiles. We attributed the observed changes in the mobility profiles by a clustering/declustering mechanism between the GHRH analogue ions and the gas modifiers, redefining the free energy landscape and leading to other local minima structures. Moreover, inspection of the mobility profiles as a function of the trapping time (100-500 ms) allowed for conformational interconversions toward more stable "gas-phase" structures. These experiments enabled us to outline a more detailed description of the structures and intermediates involved in the biological activity of GHRH, MR-406, and MIA-602.

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Name: The journal of physical chemistry. B
ISSN: 1520-5207
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