Shurtleff, V.W., Layton, M.E., Parish, C.A., Perkins, J.J., Schreier, J.D., Wang, Y., Adam, G.C., Alvarez, N., Bahmanjah, S., Bahnck-Teets, C.M. and Boyce, C.W. Journal of Medicinal Chemistry 67, no. 5 (2024): 3935-3958.
- Center for Discovery and Innovation, Hackensack Meridian Health. 111 Ideation Way. Nutley, New Jersey 07110, United States.
- Merck & Co., Inc., Rahway, New Jersey 07065, United States.
The enzymatic activity of recombinantly expressed 3CLPro enzymes from different coronaviruses was measured using the following synthetic quenched FRET peptide: CP488-ESATLQSGLRKAK- (CPQ2)-NH2 (CPC Scientific, San Jose, CA.
Curreli, Francesca, Sofia MB Victor, Shahad Ahmed, Aleksandra Drelich, Xiaohe Tong, Chien-Te K. Tseng, Christopher D. Hillyer, and Asim K. Debnath. Mbio 11, no. 6 (2020): e02451-20.
We have synthesized (CPC Scientific, Inc.) four stapled peptides, as depicted in Figure 2. We also synthesized the linear peptide, NYBSP-C, as a control. Besides, we purchased a linear peptide, SBP1, to use as a control, which was reported recently to bind to SARS-CoV-2 RBD with high affinity (KD = 47nM).
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.
Solowiej, J., Thomson, J.A., Ryan, K., Luo, C., He, M., Lou, J. and Murray, B.W. Biochemistry 47, no. 8 (2008): 2617-2630.
- Pfizer Global Research and DeVelopment, La Jolla, Pfizer Inc., 10777 Science Center Drive, San Diego, California 92121.
Peptide 4 [Dabcyl-KTSAVLQSGFRKME-Edans], peptide 5 [SITSAVLQ-pNA], and peptide 6 [SITSAVLQ-pNP] were purchased from CPC Scientific (San Jose, CA) and had the following purities: >95%, >93%, and >90.1%, respectively.
