Question

I'm simply just supposed to provide a qualitative explanation for the observation shown based on the knowledge of inter/intramolecular forces that affect protein folding.

Bonus (5 points possible): Guanidinium chloride (Gdm•HCl, structure below) and similar chemically denaturing agents of proteins are classified as chaotropic agents. Chaotropic agents disrupt the hydrogen bonding network between water molecules and/or water and hydrogen-bonding groups in proteins, including backbone amides. Side- chain cross-links in peptides have been shown to decrease the susceptibility of the peptide to chemical denaturation. For example, formation of side-chain cross-links within the villin headpiece domain (VHP) using three different cross-linking strategies exhibited a reduction in denaturant susceptibility (m) relative to the linear peptide. Data is provided below (Horne et al., Org. Biomol. Chem., 2016, 14, 5768); however, you are not required to address this data quantitatively. Briefly provide a qualitative explanation for this observation based on your knowledge of inter/intramolecular forces that affect protein folding. NH2 ci i IN HNNH2 OH Peptide Fa, m (+/- , m (+/- error) error) Guanidinium chloride 2 0.74 0.04 0.66 0.02 3 0 .73 +0.02 0.57 0.03 4 0.69 +0.04 0.58 +0.06 y YN HNSO HNA HOH Peptide Model System Cross-Linking Chemistry

Answer 1

The qualitative explanation of the above-mentioned information about the guanidinium hydrochloride is -
lel h Guanidium chloude is a chaotropic agent - that can disrupt the hydrogen bonding network between water molecules. NH Il cl® NH₂ crystal structure consists of network of guanidinium cations and chloridessous linked by N-H...d Hydrge H₂N bonds. Gu HCL It is one of the strongest denaturants in which proteus on mcleic acids lose the quaternary structure, tertiary it sewendary present in their native stage. At high concentrations of guanidinium chloride (6M), proteine like their ordered structure, & they tend to become randomly coiled. , side chan coss links in peptides have shown to decrease the susceptibility of peptide denaturation : 4A Hfold T Days AA Sfold I AA Gfolds cutselinking site Qu l Peptide model system formation of side chain links within the VHP (villin headpeace domain) using three different cross-linking strategies kalbited a reduction in denatened sucespitibility in relative to the lineas pauttle Peptide cose linking is used as a means of constraining short sequences into ences into stable folded conformations incl x-helix -

• stabilization in all three ersten arises entirely from a reduction in the entopie penalty of folding that more than compensate for an enthalpic destabilization of the folded state N = N. = stw } f or _N10-} most stablizing least stabilizing 20