The comparison of the three derivatives, together with native DB (WNWTKRF) and published non-natural derivative D16 (WNWSKAF) enabled us to study the effect of changing L-serine at position 6 to either L-arginine or apolar L-alanine. Additionally, increased activity for DB and D4 (WNWTKSF) compared to DA motivated the exchange of L-serine to L-threonine at position 4. The impressive improvement in activity due to replacing the terminal L-phenylalanine with an L-tryptophan led to the design of more derivatives derived from D9 with varying amino acids at positions 4 and 6. Consequently, derivatives D22 to D25 and D36 to D38 carrying L-arginine, L-histidine, L-serine, L-alanine, L-lysine or L-threonine on position 6 and L-threonine on position 4, as present in the more active DB, were altered to evaluate the influence of each position. Replacing L-serine at position 4 with L-alanine, appeared to have less impact on activity, as observed in D14 (WNWAKSF), possibly due to the lack of direct side-chain interaction of position 4 (Figure ). To further study the influence of position 4, D29 to D32 were designed, which correspond to related D22 to D24 and D6.