Hands matter

Section 3 of 4

In lesson 7 you saw that your proteins are built from L amino acids, so they are handed. The pocket in a target protein is handed too, and one hand of a medicine often fits it far better than the other.

Picture a pocket with three spots that each match one group on a medicine's stereocentre: a spot that makes a hydrogen bond with -⁠OH, an oily spot for -⁠CH₃, and a spot that suits -⁠NH₂. One hand of the medicine can rest all three groups on their spots at once. Its mirror image has two of those groups swapped round. However you turn it, it never matches all three spots at the same time.

One hand fits all three spots, its mirror image fits one Two ball-and-stick molecules either side of a dashed mirror line, each above the floor of a protein pocket. Each has a carbon atom with a hydrogen pointing up and three groups pointing down: OH in red, CH3 in amber and NH2 in blue, the CH3 on a wedge toward you. The pocket floor has three matching spots: red, amber, blue from left to right. On the left, every group sits on its own spot: all three fit. On the right, the mirror image, OH and NH2 have swapped sides, so only the CH3 sits on its spot. OH CH₃ NH₂ pocket all three fit NH₂ CH₃ OH pocket only one fits
One hand of a molecule rests all three groups on their matching spots in the pocket. Its mirror image has -⁠OH and -⁠NH₂ swapped, and only one group finds its spot.

Ibuprofen again

Ibuprofen eases pain the same way aspirin does, by blocking the COX enzyme. It sits in the channel into the active site and lets go again, with no bond to the enzyme. The (S) hand fits the channel well, so it is the hand that eases pain. Your body, as you have seen, turns much of the (R) hand into the (S) hand, so a tablet with both hands still works.

Levodopa

In Parkinson's disease, the nerve cells in the brain that make dopamine, a messenger molecule, slowly die. Without enough dopamine, moving becomes slow and stiff. Dopamine in the blood stays out of the brain. Levodopa, an amino acid, passes into the brain, where an enzyme turns it into dopamine.

Levodopa (L-DOPA), C₉H₁₁NO₄An amino acid, the L hand of DOPA. A benzene ring with two -OH groups on neighbouring corners, joined through a -CH₂- group to a carbon that carries an -NH₂ group, a -COOH group and a hydrogen atom.OHOHOHONH2
Levodopa, C₉H₁₁NO₄, the L hand of DOPA. Its stereocentre is the carbon carrying -⁠NH₂, -⁠COOH and a hydrogen, as in alanine. The 3D model shows the L hand.

Like alanine, DOPA comes in two hands. Amino acids keep an older naming for their hands, L and D; levodopa is the (S) hand. The enzyme that turns DOPA into dopamine works on the L hand. In 1967 doctors treated people with large doses of a mixture of both hands. The benefit came from the L hand alone, and the pure L hand, used from 1969, needed half the dose and gave fewer side effects, so the medicine today is the L hand only.

Hands in three medicines
MedicineUsed forHands in the tablet
ibuprofenpain and swellingboth, in equal amounts
naproxenpain and swelling(S) only
levodopaParkinson's diseaseL only

Today, chemists making a new medicine with a stereocentre test each hand on its own, and most new medicines of this kind are made as a single hand.

Quick check

Doctors give levodopa, the L hand of DOPA, on its own. Why?