"CATH-2 and LL-37 were synthesized by Fmoc-chemistry at CPC Scientific (Sunnyvale, CA)."
Abstract
Activation of the immune system needs to be tightly regulated to provide protection against infections and, at the same time, to prevent excessive inflammation to limit collateral damage to the host. This tight regulation includes regulating the activation of TLRs, which are key players in the recognition of invading microbes. A group of short cationic antimicrobial peptides, called cathelicidins, have previously been shown to modulate TLR activation by synthetic or purified TLR ligands and may play an important role in the regulation of inflammation during infections. However, little is known about how these cathelicidins affect TLR activation in the context of complete and viable bacteria. In this article, we show that chicken cathelicidin-2 kills Escherichia coli in an immunogenically silent fashion. Our results show that chicken cathelicidin-2 kills E. coli by permeabilizing the bacterial inner membrane and subsequently binds the outer membrane-derived lipoproteins and LPS to inhibit TLR2 and TLR4 activation, respectively. In addition, other cathelicidins, including human, mouse, pig, and dog cathelicidins, which lack antimicrobial activity under cell culture conditions, only inhibit macrophage activation by nonviable E. coli In total, this study shows that cathelicidins do not affect immune activation by viable bacteria and only inhibit inflammation when bacterial viability is lost. Therefore, cathelicidins provide a novel mechanism by which the immune system can discriminate between viable and nonviable Gram-negative bacteria to tune the immune response, thereby limiting collateral damage to the host and the risk for sepsis.
SOCIAL MEDIA
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Solid-phase peptide synthesis (SPPS) has many advantages over liquid-phase peptide synthesis (LPPS) for preparing and manufacturing synthetic peptides. Except the synthesis of short peptide sequences (i.e., less than five amino acid residues), SPPS is faster, more efficient, and more economical than liquid-phase peptide synthesis (LPPS). Some of the advantages of SPPS include: (1) Excess reagents and products can be easily washed away, (2) using excess reagents to increase reaction rates and drive reactions to completion, (3) intermediates do not require isolation or characterization, (4) access to a broader range of solvents with low volatility and high polarity, (5) tethered peptide provides a ‘pseudo-dilute’ microenvironment, which can inhibit intermolecular reactions, making some modifications easier to accomplish, and (6) compatibility with automated synthesis technology.
Lo, J.H., Hao, L., Muzumdar, M.D., Raghavan, S., Kwon, E.J., Pulver, E.M., Hsu, F., Aguirre, A.J., Wolpin, B.M., Fuchs, C.S. and Hahn, W.C. Molecular Cancer Therapeutics 17, no. 11 (2018): 2377-2388.
pTP-TAMRA-iRGD (CH3(CH)15-[GWTLNSAGYLLGKINLKALAALAKKIL-GGK(TAMRA)GGCRGDKGPDC, Cys-Cys bridge]) used in all figures except Fig. S1 was synthesized by CPC Scientific.
Ng, Ee Xien, Myat Noe Hsu, Guoyun Sun, and Chia-Hung Chen. Methods in Enzymology 628 (2019): 59-94.
The peptide sequences of the four FRET-based substrates ([..] CPC Scientific) are as follows: UV: AlexaFluor405-Leu-Ala-Gln-Ala-HompheArg-Ser-Lys (QSY35)-NH2; Blue: Dabcyl-Gly-Pro-Leu-Gly-Met-Arg-Gly-Lys (5-FAM)-NH2; Green: QSY7-Ala-Pro-Phe-Glu..
West, J.A., Tsakmaki, A., Huang, J.H., Ghosh, S.S., Parkes, D.G., Wismann, P., Rigbolt, K.T., Pedersen, P.J., Pavlidis, P., Maggs, D. and Lopez-Talavera, J.C. bioRxiv (2019) 822122.
- Fractyl Laboratories Inc, Lexington, MA, 02421, USA
- Diabetes Research Group, School of Life Course Sciences, Faculty of Life Science and Medicine, King’s College London, London, WC2R 2LS, England, UK
[..] infusion of vehicle 2 via osmotic minipump; (2) glucagon-like peptide-1 receptor (GLP-1R) agonist (0.2 mg/kg liraglutide, SC, QD, Victoza (Novo Nordisk, Bagsværd, Denmark) and continuous infusion of vehicle 2 via osmotic minipump; (3) vehicle 1 (SC, QD) and continuous infusion of a glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist (∼4.5 mg/kg/day / 56.8 nmol/kg/h GIP[3-30]NH2, CPC Scientific Inc, Sunnyvale, CA, USA) via osmotic minipump;
Artur Javmen, Vladimir Y. Toshchakov, et al. Journal of Leukocyte Biology (2019).
All CPDPs included the N‐terminal Antennapedia homeodomain sequence RQIKIWFQNRRMKWKK.38 The Cy3‐labeled peptides were produced by CPC Scientific (Sunnyvale, CA, USA). The Cy3 label was placed at the peptide N‐terminus..
Gilles, Maud-Emmanuelle, Slack, Frank J, et al. Oncotarget, 2019, Vol. 10, (No. 51), pp: 5349-5358
"Tandem peptide (pTP-iRGD: CH3(CH)15-GWTLNSAGYLLGKINLKALAALAKKIL-GGK(TAMRA)GGCRGDKGPDC, Cys-Cys bridge) was synthesized by CPC Scientific."
Garner, Thomas P., Dulguun Amgalan, Denis E. Reyna, Sheng Li, Richard N. Kitsis, and Evripidis Gavathiotis. Nature Chemical Biology 15, no. 4 (2019): 322.
"Hydrocarbon-stapled peptides corresponding to the BH3 domain of BIM, BIM SAHBA2: N-acetylated- and FITC-Ahx-EIWIAQELRS5IGDS5FNAYYA-CONH2, where S5 represents the non-natural amino acid inserted for olefin metathesis, were synthesized, purified at >95% purity by CPC Scientific Inc. and characterized as previously described."
Gibbs, Ebrima, Judith M. Silverman, Beibei Zhao, Xubiao Peng, Jing Wang, Cheryl L. Wellington, Ian R. Mackenzie, Steven S. Plotkin, Johanne M. Kaplan, and Neil R. Cashman. Scientific Reports 9, no. 1 (2019): 1-14.
The conformational epitope was synthesized as a cyclic peptide with additional N-terminal residues CG and a C-terminal G to recapitulate the predicted structure of HHQK on AβO. Peptide synthesis was performed by CPC Scientific Inc. (Sunnyvale CA, USA) [..] Cyclization was performed via a head-to-tail (C-G) amide bond and c[CGHHQKG] was then conjugated to either keyhole limpet hemocyanin (KLH) or bovine serum albumin (BSA) via maleimide-based coupling.
SUNNYVALE, US. and Hangzhou, China, June 24th, 2019 /CPCNewswire/ — CPC Scientific Inc. and its affiliate Chinese Peptide Company, a public Hangzhou-based CDMO (Stock Symbol: 002390) is pleased to announce today that their GMP manufacturing facility, has successfully passed its inspection by the competent authority of Germany as an“active substance manufacturer that has been inspected […]