Synthesis by native chemical ligation and crystal structure of human CCL2

<div> <p><a>Aureocin A53 (AucA) and lacticin Q (LnqQ) are class IId bacteriocins that display broad-spectrum activity against Gram-positive bacteria in the nanomolar range, of which their modes of action is unclear and their synthesis has not been reported. Here, we reported the chemical synthetic routes of AucA and LnqQ, enabled through the technique of native chemical ligation. To demonstrate the versatility of the syntheses, we prepared their enantiomeric counterparts, </a>D-AucA and D-LnqQ, comprised of entirely D-amino acids. X-ray crystal structure of AucA obtained through racemic protein crystallography at 1.13 Å indicates unique Lys-Trp-sulfate network. This work lays foundations for gaining further mechanistic insights into these potent bacteriocins through total chemical synthesis. </p> </div> <br>

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Total Chemical Synthesis of Aureocin A53, Lacticin Q and Their Enantiomeric Counterparts

10.26434/chemrxiv.12444554 ◽

2020 ◽

Author(s):

Alexander J. Lander ◽

Xuefei Li ◽

Yi Jin ◽

Louis YP Luk

Keyword(s):

Crystal Structure ◽

Chemical Synthesis ◽

Native Chemical Ligation ◽

Chemical Ligation ◽

X Ray ◽

Gram Positive Bacteria ◽

Spectrum Activity ◽

Synthetic Routes ◽

Nanomolar Range ◽

Broad Spectrum Activity

<div> <p><a>Aureocin A53 (AucA) and lacticin Q (LnqQ) are class IId bacteriocins that display broad-spectrum activity against Gram-positive bacteria in the nanomolar range, of which their modes of action is unclear and their synthesis has not been reported. Here, we reported the chemical synthetic routes of AucA and LnqQ, enabled through the technique of native chemical ligation. To demonstrate the versatility of the syntheses, we prepared their enantiomeric counterparts, </a>D-AucA and D-LnqQ, comprised of entirely D-amino acids. X-ray crystal structure of AucA obtained through racemic protein crystallography at 1.13 Å indicates unique Lys-Trp-sulfate network. This work lays foundations for gaining further mechanistic insights into these potent bacteriocins through total chemical synthesis. </p> </div> <br>

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Divergent Protein Synthesis of Bowman–Birk Protease Inhibitors, their Hydrodynamic Behavior and Co-crystallization with α-Chymotrypsin

Synlett ◽

10.1055/s-0036-1588840 ◽

2017 ◽

Vol 28 (15) ◽

pp. 1901-1906 ◽

Cited By ~ 4

Author(s):

Christian Tornøe ◽

Eva Johansson ◽

Per-Olof Wahlund

Keyword(s):

Crystal Structure ◽

Protein Synthesis ◽

Trypsin Inhibitor ◽

Native Chemical Ligation ◽

Protein Fold ◽

Hydrodynamic Behavior ◽

Chemical Ligation ◽

Synthesis Strategy ◽

Self Association ◽

Binding Loop

A divergent protein synthesis strategy was executed to effectively synthesize Bowman–Birk protease inhibitor (BBI) analogues using native chemical ligation of peptide hydrazides. Grafting selected residues from a potent trypsin inhibitor, sunflower trypsin inhibitor-1, onto the α-chymotrypsin-binding loop of BBI, resulted in a fourfold improvement of α-chymotrypsin inhibition. The crystal structure of a synthetic BBI analogue co-crystallized with α-chymotrypsin confirmed the correct protein fold and showed a similar overall structure to unmodified BBI in complex with α-chymotrypsin. Dynamic light scattering showed that C-terminal truncation of BBI led to increased self-association.

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Native Chemical Ligation‐Based Fluorescent Probes for Cysteine and Aminopeptidase N using meso‐thioester‐BODIPY

Chemistry - A European Journal ◽

10.1002/chem.202101990 ◽

2021 ◽

Author(s):

Youngmi Kim ◽

Uisung Lee ◽

Tae-Il Kim ◽

Sungjin Jeon ◽

Yongyang Luo ◽

...

Keyword(s):

Fluorescent Probes ◽

Aminopeptidase N ◽

Native Chemical Ligation ◽

Chemical Ligation

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Autocatalytic and oscillatory reaction networks that form guanidines and products of their cyclization

Nature Communications ◽

10.1038/s41467-021-23206-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Alexander I. Novichkov ◽

Anton I. Hanopolskyi ◽

Xiaoming Miao ◽

Linda J. W. Shimon ◽

Yael Diskin-Posner ◽

...

Keyword(s):

Chemical Cues ◽

Native Chemical Ligation ◽

Reaction Networks ◽

Oscillatory Reaction ◽

Experimental Conditions ◽

Chemical Ligation ◽

Chemical Systems ◽

Life On Earth ◽

Emergence Of Life ◽

Equilibrium Chemical

AbstractAutocatalytic and oscillatory networks of organic reactions are important for designing life-inspired materials and for better understanding the emergence of life on Earth; however, the diversity of the chemistries of these reactions is limited. In this work, we present the thiol-assisted formation of guanidines, which has a mechanism analogous to that of native chemical ligation. Using this reaction, we designed autocatalytic and oscillatory reaction networks that form substituted guanidines from thiouronium salts. The thiouronium salt-based oscillator show good stability of oscillations within a broad range of experimental conditions. By using nitrile-containing starting materials, we constructed an oscillator where the concentration of a bicyclic derivative of dihydropyrimidine oscillates. Moreover, the mixed thioester and thiouronium salt-based oscillator show unique responsiveness to chemical cues. The reactions developed in this work expand our toolbox for designing out-of-equilibrium chemical systems and link autocatalytic and oscillatory chemistry to the synthesis of guanidinium derivatives and the products of their transformations including analogs of nucleobases.

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