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¦Â-Turns are secondary structure elements not only exposed on protein surfaces, but also frequently found to be buried in protein-protein interfaces. Protein engineering so far considered mainly the backbone-constraining properties of synthetic ¦Â-turn mimics as parts of surface-exposed loops. A ¦Â-turn mimic, Hot¨TTap, that is available in gram amounts, provides two hydroxyl groups that enhance its turn-inducing properties besides being able to form side-chain-like interactions. NMR studies on cyclic hexapeptides harboring the Hot¨TTap dipeptide proved its strong ¦Â-turn-inducing capability. Crystallographic analyses of the trimeric fibritin-foldon/Hot¨TTap hybrid reveal at atomic resolution how Hot¨TTap replaces a ¦ÂI'-turn by a ¦ÂII'-type structure. Furthermore, Hot¨TTap adapts to the complex... protein environment by participating in several direct and water-bridged interactions across the foldon trimer interface. As building blocks, ¦Â-turn mimics capable of both backbone and side-chain mimicry may simplify the design of synthetic proteins.

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