A cyclic 11-MUA adhesion peptide (CPC Scientific Inc., Sunnyvale, CA) was also synthesized via standard Fmoc chemistry and cyclized via a lactam bond between Asp(1) and Lys(9) to form (11-MUA)-GG-PEG 2 -cyclo(DMGDGRPRK)-NH 2 or 11-MUA-cyclic (7C-1).
Abstract
Human pluripotent stem cells harbor an unlimited capacity to generate therapeutically relevant cells for applications in regenerative medicine. However, to utilize these cells in the clinic, scalable culture systems that activate defined receptors and signaling pathways to sustain stem cell self-renewal are required; and synthetic materials offer considerable promise to meet these needs. De novo development of materials that target novel pathways has been stymied by a limited understanding of critical receptor interactions maintaining pluripotency. Here, we identify peptide agonists for the human pluripotent stem cell (hPSC) laminin receptor and pluripotency regulator, α6-integrin, through unbiased, library-based panning strategies. Biophysical characterization of adhesion suggests that identified peptides bind hPSCs through α6-integrin with sub-μM dissociation constants similar to laminin. By harnessing a high-throughput microculture platform, we developed predictive guidelines for presenting these integrin-targeting peptides alongside canonical binding motifs at optimal stoichiometries to generate nascent culture surfaces. Finally, when presented as self-assembled monolayers, predicted peptide combinations supported hPSC expansion, highlighting how unbiased screens can accelerate the discovery of targeted biomaterials.
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 […]