Structural Variants of a Liver Fluke Derived Granulin Peptide Potently Stimulate Wound Healing
JOURNAL OF MEDICINAL CHEMISTRY
Authors: Dastpeyman, Mohadeseh; Bansa, Paramjit S.; Wilson, David; Sotillo, Javier; Brindley, Paul J.; Loukas, Alex; Smout, Michael J.; Daly, Norelle L.
Abstract
Granulins are a family of growth factors involved in cell proliferation. The liver-fluke granulin, Ov-GRN-1, isolated from a carcinogenic liver fluke Opisthorchis viverrini, can significantly accelerate wound repair in vivo and in vitro. However, it is difficult to express Ov-GRN-1 in recombinant form at high yield, impeding its utility as a drug lead. Previously we reported that a truncated analogue (Ov-GRN(12-35_3s)) promotes healing of cutaneous wounds in mice. NMR analysis of this analogue indicates the presence of multiple conformations, most likely as a result of proline cis/trans isomerization. To further investigate whether the proline residues are involved in adopting the multiple confirmations, we have synthesized analogues involving mutation of the proline residues. We have shown that the proline residues have a significant influence on the structure, activity, and folding of Ov-GRN(12-35_3s). These results provide insight into improving the oxidative folding yield and bioactivity of Ov-GRN(12-35_3s) and might facilitate the development of a novel wound healing agent.
Computational Insights into the Interaction between Li2S/Li2S2 and Heteroatom-Doped Graphene Materials
CHEMISTRYSELECT
Authors: Yi, Zonglin; Su, Fangyuan; Cui, Guangyu; Han, Peide; Dong, Nan; Chen, Chengmeng
Abstract
Electrochemical nucleation and deposition of Li2S/Li2S2 is among the major problems hindering the application of lithium-sulfur batteries. Adsorption behavior of Li2Sx (x=1, 2, 4, 8) with nitrogen-doped, boron-doped graphene and reduced graphene oxides (r-GOs) are investigated in this study by DFT method. It is discovered that graphene with pyridinic N doping (PD-N) and pyrrolic N doping (PL-N) are able to benefit the nucleation for short-chain lithium-polysulfides (Li2S/Li2S2) through Li-N interaction. r-GOs can also enhance the nucleation to some extent through Li-O interaction, which is not as good as Li-N interaction. At the same time, pristine graphene, graphene with graphitic N (GRN) and B-doped graphene can only provide Li-C interaction, which is weaker than Li-O and Li-N. This makes the sequence of adsorption strength to be PD-N approximate to PL-D>r-GO>B>GRN approximate to pristine graphene. The unique mechanism of B-doped graphene adsorbed with Li2S/Li2S2 is also discovered.