1. New alloferon analogues: synthesis and antiviral properties
Mariola Kuczer, Anna Majewska, Renata Zahorska Chem Biol Drug Des. 2013 Feb;81(2):302-9. doi: 10.1111/cbdd.12020. Epub 2012 Nov 19.
We have extended our study on structure/activity relationship studies of insect peptide alloferon (H-His-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH) by evaluating the antiviral effects of new alloferon analogues. We synthesized 18 alloferon analogues: 12 peptides with sequences shortened from N- or C-terminus and 6 N-terminally modified analogues H-X(1)-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH, where X(1) = Phe (13), Tyr (14), Trp (15), Phg (16), Phe(p-Cl) (17), and Phe(p-OMe) (18). We found that most of the evaluated peptides inhibit the replication of Human Herpesviruses or Coxsackievirus B2 in Vero, HEp-2 and LLC-MK(2) cells. Our results indicate that the compound [3-13]-alloferon (1) exhibits the strongest antiviral activity (IC(50) = 38 μM) among the analyzed compound. Moreover, no cytotoxic activity against the investigated cell lines was observed for all studied peptides at concentration 165 μM or higher.
2. Total Synthesis of Alloviroidin
Carol M Taylor, Samuel K Kutty, Benson J Edagwa Org Lett. 2019 Apr 5;21(7):2281-2284. doi: 10.1021/acs.orglett.9b00567. Epub 2019 Mar 12.
Alloviroidin is a cyclic heptapeptide, produced by several species of Amanita mushrooms, that demonstrates high affinity for F-actin as is characteristic of virotoxins and phallotoxins. Alloviroidin was synthesized via a [3 + 4] fragment condensation of Fmoc-d-Thr(OTBS)-d-Ser(OTBS)-(2 S,3 R,4 R)-DHPro(OTBS)2-OH and H-Ala-Trp(2-SO2Me)-(2 S,4 S)-DHLeu(5-OTBS)-Val-OMe to form bond A. The linear heptapeptide favored a turn conformation, facilitating cyclization between Val1 and d-Thr2 (position B). Global deprotection and HPLC purification afforded alloviroidin with NMR spectra in excellent agreement with the natural product.
3. Renin cleavage of a human kidney renin substrate analogous to human angiotensinogen, H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Ser-OH, that is human renin specific and is resistant to cathepsin D
M Poe, J K Wu, T Y Lin, K Hoogsteen, H G Bull, E E Slater Anal Biochem. 1984 Aug 1;140(2):459-67. doi: 10.1016/0003-2697(84)90194-5.
A synthetic tetradecapeptide, H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Ser-OH, which corresponds to the 13 amino terminal residues of human angiotensinogen plus a carboxy terminal serine to replace a suggested site of carbohydrate attachment, has been shown to be a good substrate for human kidney renin. At pH 7.2 and 37 degrees C the KM or Michaelis constant was 8.4 +/- 2.9 microM, and the VM or velocity at infinite tetradecapeptide concentration was 11.3 +/- 2.4 mumol angiotensin I made per hour per milligram renin. The tetradecapeptide was highly resistant to cleavage by mouse submaxillary renin. The tetradecapeptide was also slowly cleaved by human liver cathepsin D, by rabbit lung angiotensin-converting enzyme, and by reconstituted human serum, but did not yield angiotensin I. Thus, this synthetic renin substrate should permit more specific measurement of human kidney renin activity.
