TABLE 2.

Affinities of insulin, proinsulin, and analogs

	Insulin	Proinsulin (hpi)a	l-SerB8-hpi	d-AlaB8-hpi	l-AlaB8-hpib
Kd (nm)c	0.054 ± 0.008	4.1 ± 0.6	2.1 ± 0.3	∼1500	124 ± 27

^a hpi, human proinsulin.

^b The following findings together suggest that the [l-Ala^B8]proinsulin is folded correctly: the relative potencies of l-Ala^B8-DKP-insulin/l-Ser^B8-DKP-insulin and of l-Ala^B8-proinsulin/l-Ser^B8-proinsulin are closely similar; for l-Ser^B8-DKP-insulin, the disulfide pairing in the folded structure has been authenticated by two-dimensioinal NMR structural analysis; the qualitative features of the NMR spectrum of l-Ala^B8-DKP-insulin closely resemble those of the l-Ser^B8 analog.

^c Receptor-binding affinities were measured in vitro using the B isoform of the insulin receptor (IR-B) by competitive displacement of ¹²⁵I-Tyr^A14-insulin as described (28, 29).