What reason might there be for the decrease in the enthalpic favorability of folding following cross-link formation? Is there a way that you can envision to test this hypothesis?

1) Why were different cross-linking chemistries examined? Is there a clear advantage to one strategy over another?
2) What are the considerations for the synthesis of each version of the cross-linked peptides? Does one sort of chemistry appear to be more applicable in complex biological environments?
3) What reason might there be for the decrease in the enthalpic favorability of folding following cross-link formation? Is there a way that you can envision to test this hypothesis?
4) General comment

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