Site-specific fluorescein labeling of human insulin.

Three fluorescein derivatives of human insulin (HI, 1) labeled at positions N(αA1) , N(αB1) and N(εB29) respectively, were synthesized using an N-trifluoroacetyl-based protecting group scheme. The Tfa protecting group introduced by reaction with ethyl trifluoroacetate was found to be stable in aqueous and organic media and efficiently removed under mild basic conditions.

pI-shifted insulin analogs with extended in vivo time action and favorable receptor selectivity.

A long-acting (basal) insulin capable of delivering flat, sustained, reproducible glycemic control with once daily administration represents an improvement in the treatment paradigm for both type 1 and type 2 diabetes. Optimization of insulin pharmacodynamics is achievable through structural modification, but often at the expense of alterations in receptor affinity and selectivity. A series of isoelectric point (pI)-shifted insulin analogs based on the human insulin sequence or the GlyA21 acid stable variant were prepared by semi-synthetic methods.