A general method for chemogenetic control of peptide function

Protein-Based Tools for Studying Neuromodulation

“…2 We also demonstrated CAPs' ability to cage the nucleus localization signal peptide for shield-1-dependent translocation of a protein to the nucleus 2 and the seven amino acid-SsrA peptide that dimerizes with SspB protein to achieve shield-1dependent protein dimerization. 2 Further, we showed that CapC cages the C-terminal portion of enkephalin, an opioid receptor peptide agonist, to achieve shield-1-dependent activation of MOR that leads to a decrease of cAMP level (Figure 5D,E). 2 Last, we showed that CAPs-caged SsrA can be used to control transcription factor reconstitution and transcription of a reporter gene (Figure 5F) with a shield-1dependence of up to 150-fold in cell cultures.…”

“…We demonstrated the generality of the CAPs system in controlling the activity of four peptides in HEK293T cells. 2 We demonstrated that CAPs can cage the protease cleavage site TEVcs and achieve shield-1-dependent protease cleavage. 2 We also demonstrated CAPs' ability to cage the nucleus localization signal peptide for shield-1-dependent translocation of a protein to the nucleus 2 and the seven amino acid-SsrA peptide that dimerizes with SspB protein to achieve shield-1dependent protein dimerization.…”

“…2 We demonstrated that CAPs can cage the protease cleavage site TEVcs and achieve shield-1-dependent protease cleavage. 2 We also demonstrated CAPs' ability to cage the nucleus localization signal peptide for shield-1-dependent translocation of a protein to the nucleus 2 and the seven amino acid-SsrA peptide that dimerizes with SspB protein to achieve shield-1dependent protein dimerization. 2 Further, we showed that CapC cages the C-terminal portion of enkephalin, an opioid receptor peptide agonist, to achieve shield-1-dependent activation of MOR that leads to a decrease of cAMP level (Figure 5D,E).…”

“…67 Via yeast cell surface display, we selected peptide binding sequences that can bind to the ligand binding pocket of FKBP12 (F36V) such that a peptide that is directly fused to the binding sequence will be sterically blocked until shield-1 addition (Figure 5B,C). 2 Since CapN and CapC can block the accessibility of the N-and C-terminal portion of a peptide, CapN and CapC can be used together to cage both terminal portions of a peptide to achieve high chemical dependence. We demonstrated the generality of the CAPs system in controlling the activity of four peptides in HEK293T cells.…”

Rapid Formation of Intramolecular Disulfide Bridges using Light: An Efficient Method to Control the Conformation and Function of Bioactive Peptides

“…They serve many important biological functions, such as activating cell membranes, − inhibiting protein–protein interactions, , regulating protein degradation, and so on. As such, temporarily masking the activity of a peptide and restoring it upon external stimuli, such as light or small molecules, provides a powerful tool for dissecting complex biological processes and developing prodrug therapies. − The most widely employed approach to access caged peptides is side-chain caging at the active site (Scheme A). − However, as many peptides do not have well-defined active sites, in many cases, altering their function with a single side-chain caging could be roundabout and difficult to predict. Since the structure is often closely linked to the function, a possible solution to such limitation is to control the function of peptides by altering their global conformation (Scheme A).…”