Investigating Bicyclobutane–Triazolinedione Cycloadditions as a Tool for Peptide Modification

2022 ◽  
Author(s):  
Brett D. Schwartz ◽  
Aidan P. Smyth ◽  
Philippe E. Nashar ◽  
Michael G. Gardiner ◽  
Lara R. Malins
Keyword(s):  
Peptide Modification

scholarly journals Intra- and Interspecies Signaling betweenStreptococcus salivarius and Streptococcus pyogenes Mediated by SalA and SalA1 Lantibiotic Peptides

2001 ◽  
Vol 183 (13) ◽  
pp. 3931-3938 ◽  
Author(s):  
M. Upton ◽  
J. R. Tagg ◽  
P. Wescombe ◽  
H. F. Jenkinson
Keyword(s):  
Streptococcus Pyogenes ◽  
Response Regulator ◽  
Genetic Locus ◽  
Two Component System ◽  
Peptide Modification ◽  
Insertional Inactivation ◽  
Two Component ◽  
Genes Encoding ◽  
Dose Dependent

ABSTRACT Streptococcus salivarius 20P3 produces a 22-amino-acid residue lantibiotic, designated salivaricin A (SalA), that inhibits the growth of a range of streptococci, including all strains ofStreptococcus pyogenes. Lantibiotic production is associated with the sal genetic locus comprisingsalA, the lantibiotic structural gene; salBCTXgenes encoding peptide modification and export machinery proteins; andsalYKR genes encoding a putative immunity protein and two-component sensor-regulator system. Insertional inactivation ofsalB in S. salivarius 20P3 resulted in abrogation of SalA peptide production, of immunity to SalA, and ofsalA transcription. Addition of exogenous SalA peptide tosalB mutant cultures induced dose-dependent expression ofsalA mRNA (0.2 kb), demonstrating that SalA production was normally autoregulated. Inactivation of salR encoding the response regulator of the SalKR two-component system led to reduced production of, and immunity to, SalA. The sal genetic locus was also present in S. pyogenes SF370 (M type 1), but because of a deletion across the salBCT genes, the corresponding lantibiotic peptide, designated SalA1, was not produced. However, in S. pyogenes T11 (M type 4) the sallocus gene complement was apparently complete, and active SalA1 peptide was synthesized. Exogenously added SalA1 peptide from S. pyogenes T11 induced salA1 transcription in S. pyogenes SF370 and in an isogenic S. pyogenes T11salB mutant and salA transcription in S. salivarius 20P3 salB. Thus, SalA and SalA1 are examples of streptococcal lantibiotics whose production is autoregulated. These peptides act as intra- and interspecies signaling molecules, modulating lantibiotic production and possibly influencing streptococcal population ecology in the oral cavity.

scholarly journals Peptide modification results in the formation of a dimer with a 60-fold enhanced antimicrobial activity

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0173783 ◽  
Author(s):  
Amal Thamri ◽  
Myriam Létourneau ◽  
Alex Djoboulian ◽  
David Chatenet ◽  
Eric Déziel ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Peptide Modification

ChemInform Abstract: Peptide Modification by Incorporation of α-Trifluoromethyl . alpha.-Amino Acids via Trifluoromethyl-Substituted Acylimines.

ChemInform ◽  
2010 ◽  
Vol 25 (13) ◽  
pp. no-no
Author(s):  
E. HOESS ◽  
M. RUDOLPH ◽  
L. SEYMOUR ◽  
C. SCHIERLINGER ◽  
K. BURGER
Keyword(s):  
Amino Acids ◽  
Peptide Modification

scholarly journals At the confluence of ribosomally synthesized peptide modification and radicalS-adenosylmethionine (SAM) enzymology

2017 ◽  
Vol 292 (40) ◽  
pp. 16397-16405 ◽  
Author(s):  
John A. Latham ◽  
Ian Barr ◽  
Judith P. Klinman
Keyword(s):  
Peptide Modification

scholarly journals Extendable stapling of unprotected peptides by crosslinking two amines with o-phthalaldehyde

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Bo Li ◽  
Lan Wang ◽  
Xiangxiang Chen ◽  
Xin Chu ◽  
Hong Tang ◽  
...  
Keyword(s):  
Condensation Reaction ◽  
Cysteine Residue ◽  
Amino Groups ◽  
One Pot ◽  
Peptide Substrates ◽  
Peptide Chemistry ◽  
Peptide Modification ◽  
Wide Range ◽  
Sequential Addition ◽  
Aqueous Conditions

AbstractPeptide modification methods that do not rely on the cysteine residue are underdeveloped, and their development could greatly expand the current toolbox for peptide chemistry. During the course of preliminary investigations into the classical ortho-phthalaldehyde (OPA)-amine-thiol condensation reaction, we found that in the absence of thiol, OPA readily condenses with two primary alkyl amines to form a class of underexplored isoindolin-1-imine compounds under mild aqueous conditions. From the intramolecular version of this OPA-2amines reaction, an efficient and selective methodology using mild reaction conditions has been developed for stapling unprotected peptides via crosslinking of two amino groups in both an end-to-side and side-to-side fashion. The stapling method is superfast and broadly applicable for various peptide substrates with the reacting amino groups separated by a wide range of different amino acid units. The macrocyclization reactions of selected substrates are completed within 10 seconds at 5 mM concentration and within 2 minutes at 50 μM concentration. Importantly, the resulting cyclized peptides with an isoindolinimine linkage can be extended in a one-pot sequential addition manner with several different electron-deficient π electrophiles, thereby generating more complex structures.

scholarly journals Experimental and Computational Investigations into Trivalent Phosphorous-Mediated Radical Thiol Desulfurization

2021 ◽  
Author(s):  
John Lopp ◽  
Valerie Schmidt
Keyword(s):  
Atom Transfer ◽  
Radical Intermediate ◽  
Thiyl Radicals ◽  
Trigonal Bipyramidal ◽  
Peptide Modification ◽  
Aliphatic Thiols ◽  
Mechanism And Kinetics ◽  
Kinetics Of ◽  
Marked Dependence ◽  
Distorted Trigonal Bipyramidal

Radical-mediated thiol desulfurization processes using tricoordinate phosphorous reagents are used in a range of applications from small molecule synthesis to peptide modification. A combined experimental and computational examination of the mechanism and kinetics of the radical desulfurization of alkyl thiyl radicals using trivalent phosphorus reagents was performed. Primary alkyl thiols undergo desulfurization between 10^6 to 10^9 M-1s-1 depending on the phosphorus component with either an H-atom transfer step or β-fragmentation of the thiophosphoranyl intermediate may be rate-controlling. While the desulfurization of primary aliphatic thiols showed a marked dependence on the identity of phosphorous reagent used with either a rate-controlling H-atom transfer or -fragmentation, thiols yielding stabilized C-centered radicals showed much less sensitivity. Support for a stepwise S-atom transfer process progressing via a distorted trigonal bipyramidal thiophosphoranyl radical intermediate was obtained from DFT calculated energetics and hyperfine splitting values.

scholarly journals Efficient rational modification of non-ribosomal peptides by adenylation domain substitution

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mark J. Calcott ◽  
Jeremy G. Owen ◽  
David F. Ackerley
Keyword(s):  
Amide Bond ◽  
Assembly Lines ◽  
Modular Assembly ◽  
Catalytic Domains ◽  
Peptide Modification ◽  
Proof Reading ◽  
Peptide Synthetase ◽  
A Domains ◽  
High Yields ◽  
Non Ribosomal Peptides

Abstract Non-ribosomal peptide synthetase (NRPS) enzymes form modular assembly-lines, wherein each module governs the incorporation of a specific monomer into a short peptide product. Modules are comprised of one or more key domains, including adenylation (A) domains, which recognise and activate the monomer substrate; condensation (C) domains, which catalyse amide bond formation; and thiolation (T) domains, which shuttle reaction intermediates between catalytic domains. This arrangement offers prospects for rational peptide modification via substitution of substrate-specifying domains. For over 20 years, it has been considered that C domains play key roles in proof-reading the substrate; a presumption that has greatly complicated rational NRPS redesign. Here we present evidence from both directed and natural evolution studies that any substrate-specifying role for C domains is likely to be the exception rather than the rule, and that novel non-ribosomal peptides can be generated by substitution of A domains alone. We identify permissive A domain recombination boundaries and show that these allow us to efficiently generate modified pyoverdine peptides at high yields. We further demonstrate the transferability of our approach in the PheATE-ProCAT model system originally used to infer C domain substrate specificity, generating modified dipeptide products at yields that are inconsistent with the prevailing dogma.

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