3 The investigators synthesized a number of glucagon analogs

3. The investigators synthesized a number of glucagon analogs which are listed in Table 26.1. The ability of the glucagon analogs to bind to receptors and elicit a biological response was measured and compared to native glucagon. Use the information provided in the table to answer the following questions. a. What is the effect of substituting or eliminating the amino acid at position 9? b. What is the effect of the amino acid replacement or modification at position 12? c. What is the effect of the amino acid replacement at position 17? Be specific. d. What is the effect of the amino acid replacement at position 18? Be specific. e. What is the role of the histidine at position 1?

Solution

Answer:

3. (a) Replacement of amino acid at position 9 with any other residue resulted in retaining the binding capacity of the analog to the receptor, but did not stimulate cAMP production.

(b) Replacement of amino acid at position 12 resulted in a decreased binding capacity of the analog to the receptor but retained the ability to stumulate production of cAMP.

(c) Decreased binding capacity but retained the ability to stimulate cAMP production, the only exception included the substitution with Ala. The small size of Ala may contribute to the property.

(d) Decreased binding to the receptor but retained the ability to stimulate cAMP production, almost equivalent to the native glucagon.

(e) His at position 1 interacts with Asp at 9. Any modification of His at 1 along with modification at position 16 led to the potent decrease in the ability to activitate cAMP (almost 0). It also showed decreased binding.