64 • Impacts of Applied Genetics — Micro-Organisms, Plants, and Animals 
Table 4.— Naturally Occurring Small Peptides of 
Potential Medical Interest 
Number of 
amino acids 
Molecular 
weight 
Dynorphin 
17 
Little gastrin (LG) 
17 
2,178 
Somatostatin 
14 
1,639 
Bombesin 
14 
1,620 
Melanocyte stimulating hormone. 
13 
1,655 
Active dynorphin fragment 
13 
Neurotensin 
13 
Mini-gastrin (G13) 
13 
Substance? 
Luteinizing hormone-releasing 
11 
1,347 bovine 
hormone (LNRH) 
10 
1,183 
Active fragment of CCK 
10 
Angiotensin 1 
10 
1,297 
Caerulein 
10 
1,252 porcine 
Bradykinin 
9 
1,060 
'Vasopressin (ADH) 
9 
'Oxytocin 
9 
1,007 
Facteur thymique serique (FTH) . . 
9 
Substance P(4-11)octapeptide. . . 
8 
966 
Angiotensin II 
8 
1,046 
Angiotensin III 
7 
931 
MSH/ACTH4-10 
7 
Enkephalins 
Active fragment of thymopoietin 
5 
575 
(TP5) 
'Thyrotropin releasing hormone 
5 
(TRH) 
3 
362 
•Currently used in medical practice. 
SOURCE: Office of Technology Assessment. 
agents prove of value in wider testing, they 
have an enormous potential for use. 
• Both cholecystokinin (33 AA) and bomhesin 
(10 AA), which have been shown to sup- 
press appetite, presumably as a satiety 
signal from stomach to brain: there is a 
large market for antiobesity agents— ap- 
proximately $85 million per year at the 
manufacturer’s level. 
• Several hormones, such as somatostatin, 
which are released by nerves in the hypo- 
thalamus of the brain to stimulate or in- 
hibit release of hormones by the pituitary 
gland: hormones produced by these glands 
are crucial in human fertility; analogs of 
some are being investigated as possible 
contraceptives. 
• Calcitonin (32 AA), which is currently the 
largest polypeptide produced by chemical 
synthesis for commercial pharmaceutical 
use: it is useful for pathologic bone dis- 
orders, such as Paget’s disease, that affect 
up to 3 percent of the population over 40 
years of age, in Western Europe. 
• Adrenocorticotropic hormone (ACTH) (39 
AA), which promotes and maintains the 
normal growth and development of the 
adrenal glands and stimulates the secretion 
of other hormones: in the United States, 
ACTH is used primarily as a diagnostic 
agent for adrenal insufficiency, but in 
principle, ACTH might be used for at least 
one-third of the medical indications— like 
rheumatic disorders, allergic states, and 
eye inflammation— for which about 5 mil- 
lion Americans annually recei\e corticos- 
teroids. 
Within the last 5 years, other small polypep- 
tides have been identified in many tissues and 
have been linked to a \arietv of activ ities. Some 
certainly bind to the same receptor sites as the 
pain-relieving opiates related to the morphine 
family. These peptides are called endogenous 
opiates: the smaller (5 AA) peptides are called 
enkephalins and the larger (3 1 AA), endoi'phins. 
Certain enkephalins produce hi'ief analgesia 
when injected directly into the hi’ains of mice. 
Synthetic analogs that are less susceptible to en- 
zymatic inactivation produce longer analgesia 
even if they are injected intravenously, as does 
the larger j8-endorphin molecule. \'(M’v reccMilly, 
a 17 AA polypeptide, dynoi’phin, was r(>ported 
to be the most potent pain killer yet found— it is 
1,200 times more powerful than morphine. 
The preparation of new analgesic agents ap- 
pears a likely outcome of the ncnv research, hut 
problems similar to those associated with clas- 
sical opiates must he overcome. (T)nse(|uentl\ , 
unnatural analogs— including some made with 
amino acids not found in mici'o-organisms— 
might prove more useful. The value of microhi- 
al biosynthesis for these substances is (jiies- 
tionable at this time. Howcvcm', the im|)ortance 
of genetic technologies in clarilving the 
underlying mechanisms should tiot he undei - 
estimated. 
Higher moleculai' weight [)olv[)eptldes cannot 
be made practically by chemical synthesis, .ind 
must he exti’acted from human or animal tis 
sues or produced in cells growing in culture 
