This invention relates generally to methods of producing peptide-based anti-angiogenesis compounds using plasmin reductases, and specifically to methods of producing an A.sub.61 anti-angiogenic plasmin fragment using an annexin II heterotetramer or subunit thereof. This invention also relates to anti-angiogenesis methods and compositions comprising a plasmin reductase or polynucleotides encoding subunits thereof. Compositions useful for the inhibition or promotion of angiogenesis are also disclosed.