"The stapled peptides with greater than 90% purity were synthesized by.. CPC Scientific, CA"
Abstract
Hydrocarbon stapling of peptides is a powerful technique to transform linear peptides into cell-permeable helical structures that can bind to specific biological targets. In this study, we have used high resolution solution NMR techniques complemented by Dynamic Light Scattering to characterize extensively a family of hydrocarbon stapled peptides with known inhibitory activity against HIV-1 capsid assembly to evaluate the various factors that modulate activity. The helical peptides share a common binding motif but differ in charge, the length and position of the staple. An important outcome of the study was to show the peptides share a propensity to self-associate into organized polymeric structures mediated predominantly by hydrophobic interactions between the olefinic chain and the aromatic side-chains from the peptide. We have also investigated in detail the structural significance of the length and position of the staple, and of olefinic bond isomerization in stabilizing the helical conformation of the peptides as potential factors driving polymerization. This study presents the numerous challenges of designing biologically active stapled peptides and the conclusions have broad implications for optimizing a promising new class of compounds in drug discovery.
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Baba, Osamu, Andrew Elvington, Martyna Szpakowska, Deborah Sultan, Gyu Seong Heo, Xiaohui Zhang, Hannah Luehmann et al. bioRxiv (2020).
The FC131 peptide (cyclo[2-Nal-Gly-d-Tyr-NMe-d-Orn-Arg]) was synthesized by CPC Scientific (Sunnyvale, CA).
This guide will help you understand how to read ESI spectra for large and complex bio-molecules like peptides. Other techniques such as high-performance liquid chromatography (HPLC) show one major peak (i.e., absorbance and purity for RP-HPLC) in the spectra, making the interpretation straightforward. ESI-MS spectra are more complicated due to the multiplicity of the data. While most small molecules (100-500 AMU) behave well in ESI-MS and ionize as a single charged state, larger biomolecules, such as peptides, ionize as multiple charged variants. A major advantage of ESI-MS over other mass spectroscopy techniques is that molecular fragmentation is rare (t-Boc groups and a few other protection groups are an exception), which is why ESI-MS is often referred to as a soft ionization technique.
Vickers, Timothy A., Meghdad Rahdar, Thazha P. Prakash, and Stanley T. Crooke. Nucleic Acids Research (2019).
A solution of 1.5 umol SmBiT peptide (Val-Thr-Gly-Tyr-Arg-Leu-Phe-Glu-Glu-Ile-Leu-Gly-Gly-Ser-Gly-Gly-Lys(N3)-NH2) containing an azide group at the C-terminus (CPC Scientific, 1245 Reamwood Ave, Sunnyvale, CA, USA) in DMSO (0.5 ml) was added and the reaction mixture was stirred at room temperature for 5 h.
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."
