{'fraction_non_alphanumeric': 0.03767491926803014, 'fraction_numerical': 0.02583423035522067, 'mean_word_length': 5.118421052631579, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 2, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Branches on the α‐C Atom of Cyclosporin A Residue 3 Result in Direct Calcineurin Inhibition and Rapid Cyclophilin 18 Binding

The immunosuppressive drug cyclosporin A (CsA) is a bifunctional molecule. It directly inhibits the peptidyl-prolyl cis/trans isomerase (EC number 5.2.1.8) (PPIase) cyclophilin 18 (Cyp18), while the resulting Cyp18±CsA binary complex targets the serine/threonine phosphatase (EC number 3.1.3.3) calcineurin (CaN) through a gain-of-function mechanism. Whereas CaN inhibition is thought to be the main contribution of CsA in immunosuppression, many recent findings have also indicated essential roles of Cyp18 in various cellular events. For example, Cyp18 is required for the HIV-1 life cycle. To dissect the numerous biological effects involved in CsA treatment and distinguish the Cyp18 and CaN inhibition, the design of CsA derivatives that inhibit CaN specifically would shed new light in this field.