Given an irreducible non-spherical non-affine (possibly non-proper) building $X$, we give sufficient conditions for a group $G < Aut(X)$ to admit an infinite-dimensional space of non-trivial quasi-morphisms. The result applies to all irreducible (non-spherical and non-affine) Kac-Moody groups over integral domains. In particular, we obtain finitely presented simple groups of infinite commutator width, thereby answering a question of Valerii G. Bardakov from the Kourovka notebook. Independently of these considerations, we also include a discussion of rank one isometries of proper CAT(0) spaces from a rigidity viewpoint. In an appendix, we show that any homogeneous quasi-morphism of a locally compact group with integer values is continuous.