Insulin degludec: rationally designed, beyond sequence modification

1
Insulin degludec rationally designed, beyond
sequence modification
Des(B30) LysB29(?-Glu Ne-hexadecandioyl) human
insulin
DesB30
T
DesB30 insulin
L-?-Glu
Glutamic acid spacer
Hexadecandioyl
Fatty diacid side chain
2
Insulin degludec immediately after injection
Phenol Zn2
Insulin degludec injected
Phenol from the vehicle diffuses
quickly, and insulin degludec links up via single
side-chain contacts
Long multihexamer chains assemble
Jonassen et al. Pharm Res 201229210414
3
Insulin degludec slow release following injection
Subcutaneous depot
Zn2
Insulin degludec multihexamers
Zinc diffuses slowly causing individual hexamers
to disassemble, releasing monomers
Monomers are absorbed from the depot into the
circulation
Jonassen et al. Pharm Res 201229210414