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A lactam bridge loaded at Glu 22 , either c[Lys 18 Glu 22 ] or c[Glu 22 Lys 26 ], shows lower affinity and activity than a simple substitution of Gly 22 with Glu.28,36 Theoretically, the substitution of Gly 22 with Ala would make the -helix more stable, but increments in the affinity and activity were not found