Zn(II) is an inhibitor of SARS-CoV-2′s RNA-dependent RNA polymerase, and chloroquine and hydroxychloroquine are Zn(II) ionophores–this statement gives a curious mind a lot to think about. We show results of the first clinical trials on chloroquine (CQ) and hydroxychloroquine (HCQ) in the treatment of COVID-19, as well as earlier reports on the anticoronaviral properties of these two compounds and of Zn(II) itself. Other FDA-approved Zn(II) ionophores are given a decent amount of attention and are thought of as possible COVID-19 therapeutics.
The antimicrobial activity of surfactant-associated anionic peptides (SAAPs), which are isolated from the ovine pulmonary surfactant and are selective against the ovine pathogen Mannheimia haemolytica, is strongly enhanced in the presence of Zn(II) ions. Both calorimetry and ITC measurements show that the unique Asp-only peptide SAAP3 (DDDDDDD) and its analogs SAAP2 (GDDDDDD) and SAAP6 (GADDDDD) have a similar micromolar affinity for Zn(II), which binds to the N-terminal amine and Asp carboxylates in a net entropically-driven process. All three peptides also bind Cu(II) with a net entropically-driven process but with higher affinity than they bind Zn(II) and coordination that involves the N-terminal amine and deprotonated amides as the pH increases. The parent SAAP3 binds Cu(II) with the highest affinity; however, as shown with potentiometry and absorption, CD and EPR spectroscopy, Asp residues in the first and/or second positions distinguish Cu(II) binding to SAAP3 and SAAP2 from their binding to SAAP6, decreasing the Cu(II) Lewis acidity and suppressing its square planar amide coordination by two pH units. We also show that these metal ions do not stabilize a membrane disrupting ability nor do they induce the antimicrobial activity of these peptides against a panel of human pathogens.
Org. proceed in good yield under conditions which are not conducive to racemisation.Preparation of 2-Toluene-p-sdphonylethyl Esters of Amino-acids.-(a) By esterijcation of the hydroxysulfihone. Several sets of conditions for direct esterification were examined. In the best general procedure, the acid is converted into the N-benzyloxycarbonyl derivative which is then treated with 2-toluene-fi-sulphonylethanol and dicyclohexylcarbodi-imide in acids were converted into their 2-chloroethyl esters by the Fischer-Speier method. An acid-labile N-protecting group, trityl or benzyloxycarbonyl, was attached, and the N-protected 2-chloroethyl ester was treated with sodium toluene-p-thiolate in t-butyl alcohol. t-Butyl alcohol was used in preference to ethanol; in ethanol, transesterification occurs. The N-protecting group was then removed from the 2-$-tolylthioethyl ester. This ester salt could then be incorporated into a peptide and P*NHCHR*CO,H (I) P +NH3CHR*C0,-
Can a minor difference
in the nonmetal binding sequence of antimicrobial
clavanins explain the drastic change in the coordination environment
and antimicrobial efficiency? This study answers the question with
a definite “yes”, showing the details of the bioinorganic
chemistry of Zn(II) and Cu(II) complexes with clavanins, histidine-rich,
antimicrobial peptides from hemocytes of the tunicate
Styela
clava
.
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