"Folded Crp23 was created from a synthesized 80% pure linear peptide (CPC Scientific, Sunnyvale, CA) by the same procedure as previously reported for the α-defensin HD5"
Abstract
Organoids mirror in vivo tissue organization and are powerful tools to investigate the development and cell biology of the small intestine. However, their application for the study of host–pathogen interactions has been largely unexplored. We have established a model using microinjection of organoids to mimic enteric infection, allowing for direct examination of pathogen interactions with primary epithelial cells in the absence of confounding variables introduced by immune cells or the commensal microbiota. We investigated the impact of Paneth cell α-defensin antimicrobial peptides on bacterial growth. We demonstrate that organoids form a sealed lumen, which contains concentrations of α-defensins capable of restricting growth of multiple strains of Salmonella enterica serovar Typhimurium for at least 20 h postinfection. Transgenic expression of human defensin 5 in mouse organoids lacking functional murine α-defensins partially restored bacterial killing. We also found that organoids from NOD2−/− mice were not impaired in α-defensin expression or antibacterial activity. This model is optimized for the study of non-invasive bacteria but can be extended to other enteric pathogens and is amenable to further genetic manipulation of both the host and microbe to dissect this critical interface of host defense.
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Bueno, A.B., Sun, B., Willard, F.S., Feng, D., Ho, J.D., Wainscott, D.B., Showalter, A.D., Vieth, M., Chen, Q., Stutsman, C. and Chau, B. Nature Chemical Biology 16, no. 10 (2020): 1105-1110.
- Lilly, S.A., Alcobendas, Spain.
- ConfometRx, Santa Clara, CA, USA.
- Departments of Quantitative Biology, Discovery Chemistry Research and Technologies, and Diabetes and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
- Lilly Biotechnology Center San Diego, San Diego, CA, USA.
Peptides were synthesized and purified to >95% purity at Eli Lilly and Company or purchased from CPC Scientific or Tocris. GLP-1(9-36)NH2, GLP-1(7-36)NH2, OXM(1-37)OH and GIP(1-42)NH2 were used for pharmacology experiments, and GLP-1(7-37)OH was used for cryo-EM studies.
Marion, Vincent, and Nikolai Petrovsky. U.S. Patent Application 16/627,389, filed July 9, 2020.
H-VECTM-R8-EKRVLA-S5-LDKPPFLTQLHS-OH (SEQ ID NO: 21) [..] H-VECTM-R8-EKRVLA-S5-LDKPPFLTQLHS-NH2 [..]
SAN JOSE, CA., June 25, 2020 /CPCNewswire/ — CPC Scientific Inc., a San Jose based CDMO with GMP manufacturing facilities in Hangzhou, is pleased to announce that their drug master file (DMF) for cetrorelix acetate has been submitted to the U.S. Food and Drug Administration and has been issued DMF# 034884. This generic peptide API […]
We are very excited about the addition of the cetrorelix DMF to our growing generic peptide portfolio. Our multi-kg scale cGMP manufacturing facility for cetrorelix will provide more opportunities for IVF treatments in the medical communities and pathways to new treatments for hormone-sensitive breast and prostate cancers.
Belenkaya, S. V., A. A. Bondar, T. A. Kurgina, V. V. Elchaninov, A. Yu Bakulina, E. A. Rukhlova, O. I. Lavrik, A. A. Ilyichev, and D. N. Shcherbakov. Biochemistry (Moscow), 2020.
A synthetic peptide of the following composition was used as a substrate: Dabcyl-HPHPHLSFMAIPK (5-FAM) KK-NH2 (Dabcyl = 4-(dimethylaminoazo) benzene-4-carboxylic acid, 5-FAM = 5-carboxyfluorescein) (CPC Scientific, USA) containing the Chn-sensitive region of bovine κ-casein.
Hao, Liangliang, Renee T. Zhao, Chayanon Ngambenjawong, Heather E. Fleming, and Sangeeta Bhatia. bioRxiv (2020).
All peptides were chemically synthesized by CPC Scientific, Inc. [..] K(N3)-ANP-GPVPLSLVMGGC [..] 5FAM-GGf-Pip-KSGGGK(CPQ2)-PEG2-GC
On 28 May 2020, the European Medicines Agency (EMA), via its Committee for Medicinal Products for Human Use (CHMP), adopted a positive opinion of Hepcludex. This drug is intended for the treatment of chronic hepatitis delta virus (HDV) infection in adult patients with compensated liver disease, and effectively reduces HDV RNA levels and signs of […]
Pandya, P., Sayers, R.O., Ting, J.P., Morshedian, S., Torres, C., Cudal, J.S., Zhang, K., Fitchett, J.R., Zhang, Q., Zhang, F.F. and Wang, J. PLoS One 15, no. 6 (2020): e0233961.
- Departments of Protein Engineering, Eli Lilly Biotechnology Center, Discovery Chemistry Research and Technologies, San Diego, California, United States of America
- Departments of Structural Biology, Quantitative Biology, and Recombinant Protein Generation, Discovery Chemistry Research and Technologies, and, Eli Lilly and Company, Indianapolis, Indiana, United States of America
- Centro de Investigacio´n Lilly, Alcobendas, Spain
Peptide synthesis was outsourced to CPC Scientific.
Mutations to the RBD of SARS-CoV have resulted in the reorganization of SARS-CoV-2 RBD, specifically to the loops that are in close proximity to the ACE2-binding ridge. Due to these structural changes, an additional intramolecular main-chain hydrogen bond is gained between Asn487 and Ala475 (Figure 4a). The Asn487–Ala475 hydrogen bond causes the RBM of SARS-CoV-2 to be more structurally compact, enabling the loop containing Ala475 to move into closer proximity to the ACE2 α1 helix. Closer contact between the RBM and α1 helix of ACE2 results in more intermolecular interactions (Figure 4a,b). Some of these interactions include hydrogen bonds between Gln493 (SARS-CoV-2) and Glu35 (ACE2),[3b,c] and main-chain hydrogen bonds between Gly502 and Lys31.