Tài liệu Color Atlas of Pharmacology (Part 7): Drug-Receptor Interaction doc

Types of Binding Forces

Unless a drug comes into contact with

intrinsic structures of the body, it can￾not affect body function.

Covalent bond. Two atoms enter a

covalent bond if each donates an elec￾tron to a shared electron pair (cloud).

This state is depicted in structural for￾mulas by a dash. The covalent bond is

“firm”, that is, not reversible or only

poorly so. Few drugs are covalently

bound to biological structures. The

bond, and possibly the effect, persist for

a long time after intake of a drug has

been discontinued, making therapy dif￾ficult to control. Examples include alky￾lating cytostatics (p. 298) or organo￾phosphates (p. 102). Conjugation reac￾tions occurring in biotransformation al￾so represent a covalent linkage (e.g., to

glucuronic acid, p. 38).

Noncovalent bond. There is no for￾mation of a shared electron pair. The

bond is reversible and typical of most

drug-receptor interactions. Since a drug

usually attaches to its site of action by

multiple contacts, several of the types of

bonds described below may participate.

Electrostatic attraction (A). A pos￾itive and negative charge attract each

other.

Ionic interaction: An ion is a particle

charged either positively (cation) or

negatively (anion), i.e., the atom lacks or

has surplus electrons, respectively. At￾traction between ions of opposite

charge is inversely proportional to the

square of the distance between them; it

is the initial force drawing a charged

drug to its binding site. Ionic bonds have

a relatively high stability.

Dipole-ion interaction: When bond

electrons are asymmetrically distribut￾ed over both atomic nuclei, one atom

will bear a negative (!–), and its partner

a positive (!+) partial charge. The mole￾cule thus presents a positive and a nega￾tive pole, i.e., has polarity or a dipole. A

partial charge can interact electrostati￾cally with an ion of opposite charge.

Dipole-dipole interaction is the elec￾trostatic attraction between opposite

partial charges. When a hydrogen atom

bearing a partial positive charge bridges

two atoms bearing a partial negative

charge, a hydrogen bond is created.

A van der Waals’ bond (B) is

formed between apolar molecular

groups that have come into close prox￾imity. Spontaneous transient distortion

of electron clouds (momentary faint di￾pole, !!) may induce an opposite dipole

in the neighboring molecule. The van

der Waals’ bond, therefore, is a form of

electrostatic attraction, albeit of very

low strength (inversely proportional to

the seventh power of the distance).

Hydrophobic interaction (C). The

attraction between the dipoles of water

is strong enough to hinder intercalation

of any apolar (uncharged) molecules. By

tending towards each other, H2O mole￾cules squeeze apolar particles from

their midst. Accordingly, in the organ￾ism, apolar particles have an increased

probability of staying in nonaqueous,

apolar surroundings, such as fatty acid

chains of cell membranes or apolar re￾gions of a receptor.

58 Drug-Receptor Interaction

Lüllmann, Color Atlas of Pharmacology © 2000 Thieme

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