"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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Boehm, M., Beaumont, K., Jones, R.M., Kalgutkar, A.S., Zhang, L., Atkinson, K., Bai, G., Brown, J.A., Eng, H., Goetz, G.H. and Holder, B.R. Journal of Medicinal Chemistry (2017).
- Pfizer Worldwide Research & Development, Cambridge, Massachusetts 02139, United States
- Pfizer Worldwide Research & Development, Groton, Connecticut 06340, United States
The chemokine receptor CXCR7 is an attractive target for a variety of diseases. While several small-molecule modulators of CXCR7 have been reported, peptidic macrocycles may provide advantages in terms of potency, selectivity, and reduced off-target activity
Bainbridge, Travis W., et al. Scientific Reports 7.1 (2017): 12524.
- Protein Chemistry, Molecular Oncology, Discovery Chemistry, Cancer Immunology, and Neuroscience. Genentech Inc., South San Francisco, CA, 94080, USA
"ANP FAP and aP NIRF were synthesized by CPC Scientific (Sunnyvale, CA)… Another internally-quenched FRET peptide substrate (ANPFAP) for FAP has recently been reported and demonstrated for use as an activity-based, in vivo imaging tool. The peptide sequence contains two internal Gly-Pro dipeptide motifs, susceptible to FAP cleavage and a Cy5.5/QSY21, quenched-FRET pair."
Coorens, Maarten, et al. The Journal of Immunology 199.4 (2017): 1418-1428.
"CATH-2 and LL-37 were synthesized by Fmoc-chemistry at CPC Scientific (Sunnyvale, CA)."
Tcholakov, I., Grimshaw, C.E., Shi, L., Kiryanov, A., Murphy, S.T., Larson, C.J., Plonowski, A. and Ermolieff, J. Bioscience Reports 37, no. 3 (2017): BSR20170275.
- Departments of In Vitro Pharmacology, Immunology, Enzymology and Biophysical Chemistry, Medicinal Chemistry, External Innovation, Metabolic Disease, In Vitro Pharmacology, and Gastrointestinal and Enterology Discovery Unit, Takeda California, Inc., 10410 Science Center Drive, San Diego, CA 92121, U.S.A
The substrate used for our PHD2 kinetic study was a 17-mer peptide mimicking the sequence of HIF-1a surrounding the Pro564 residue hydroxylated by the PHD enzymes (Biotin-DLEMLAPYIPMDDDFQL). The substrate used for FIH1 was a 34-mer peptide mimicking the sequence of HIF-1α surrounding residue Asn803 (DESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRAL). Both peptides were synthesized by CPC Scientific Inc.
Wilson, Sarah S., et al. PLoS Pathogens 13.6 (2017): e1006446.
"Cryptdin 2 (UniProtKB: P28309, LRDLVCYCRTRGCKRRERMNGTCRKGHLMYTLCCR)... obtained by oxidative refolding of partially purified linear peptides (synthesized by CPC Scientific...) and purifying the correctly folded species by reverse-phase high-pressure liquid chromatography (RP-HPLC). Purity was determined by analytical RP-HPLC, and the mass of the disulfide-bonded peptides was verified by high mass accuracy liquid chromatography-mass spectrometry."
Sattiraju, A., et al. Oncotarget 2017, 8 (26), 42997-43007.
For Ac-225 labeling, the prepared DOTA-Pep-1L (CPC-scientific, San Jose, CA) was incubated with Ac-225 at 70°C for 50 minutes. The TLC plates were scanned on a BioScan Imaging Scanner. Cu-64 was purchased from Washington University in St. Louis. The custom peptide specific to IL13RA2 and a scrambled peptide were conjugated with NOTA by CPC scientific Inc (San Jose, CA). Both the peptides, Pep-1L and scrambled peptide-NOTA were radiolabeled with Cu-64 according to the previously reported methods [15].
Puthenveetil, Sujiet, et al. PloS One 12.5 (2017): e0178452.
- Worldwide Medicinal Chemistry, Pfizer Global R&D, Groton, Connecticut, United States of America.
- Pfizer Oncology Research, Pearl River, NY, United States of America.
"Peptide-payload conjugate (7) was prepared by reacting 2mM aizoacetyl-Ser-Lys-Gly-Ser-Lys (CPC scientific, inc. Sunnywale, CA) with 8 mM NHS-ester payload [19] in 50% Dimethyl sulfoxide (DMSO), 50 mM borate buffer pH 8.5 for 2 h at 37°C."
Kwon, Ester J., et al. Advanced Materials 29.35 (2017).
"[..] synthesized for initial screening with FAM-conjugated lysine at the C-terminal end of the membrane-interactive peptide and with or without D[KLAKLAK]2 on the C-terminus using standard Fmoc chemistry[..] All peptides were synthesized with N-terminal myristic acid and C-terminal amine. [..] larger quantities of the peptides were synthesized by CPC Scientific to 90% purity"
Noland, Cameron L., et al. Proceedings of the National Academy of Sciences 114.30 (2017): E6044-E6053.
- Departments of Structural Biology, Infectious Diseases, Biochemical and Cellular Pharmacology, Pathology, Translational Immunology, and Biomolecular Resource Group, Genentech, Inc., South San Francisco, CA 94080.
"..peptide substrates were synthesized based on the Pal lipoprotein, Pal peptideshort (Pam2Cys-SSNKNGGK-Biotin; CPC Scientific, Inc.).."