- The complete OWLS solutions set: OWLSsolutionstoallproblems.pdf

- Final review session TODAY led by En-wei in CS24 from 3-4:20pm- Final Exam:

- - Each part is worth 100 points and you will have a total of 3 hours to complete both parts (you can work on them in any order you choose, or go back and forth between them).

- - Part A will cover all the "new" material since Midterm 2.- - Part B will be comprehensive and will cover the

entire course. Practice on old exams! http://www.chem.ucla.edu/harding/14C/14C_s12/14C_s12_syl.html#exams

- Your final exam will be on Wednesday, June 13 from 8-11am.Last name A-C: Please go to Young 2200Last name D-Z: Please go to CS50

- You may use your model kits! You will be provided with all the information you were given on Midterm 1 and Midterm 2

Biomolecules Survey Part 4: Nucleic AcidsLecture Supplement page 248

Early History

1869: Friedrich Miescher isolates “nuclein” from white blood cells

Phosphoric acid

O

PHO

OH

OH

Heterocyclic baseHeterocycle: Has a least one ring which includes an atom other than carbon

Pyrimidines Cytosine (C) Thymine (T) DNA Uracil (U) RNA

Purines Adenine (A) Guanine (G)

N

N

N

NN

N

H

N

N

H

O

NH2

N

N

H

O

O

H3C H

N

N

H

O

O

H

N

NN

N

H

H

O

NH2N

NN

N

H

NH2

Early 20th century: Nuclein found to consist of three fundamental components

X = OH, D-riboseX = H, 2-deoxy-D-ribose

CHO

CH X

CH OH

CH OH

CH2OH

Adenosine (a nucleoside)

O

XHO

HO

N

NN

N

NH2

Nucleosides and Nucleotides

1920’s: Carbohydrate + heterocyclic base = nucleoside

•Heterocyclic base nitrogen bonded to ribofuranose anomeric carbon

•Carbohydrate = ribose (X = OH) in ribonucleic acid (RNA)

= deoxyribose (X = H) in deoxyribonucleic acid (DNA)

•Nucleoside + phosphoric acid = nucleotide (nucleoside with phosphate on 3' or 5' carbon)

Adenylic acid (a nucleotide)

orO

XHO

O

N

NN

N

NH2

PHO

O

HO

O

XO

HO

N

NN

N

NH2

P

O

HO

HO

1'2'3'

4'

5'

DNA is a Polymer1939: DNA is a polymer of many nucleosides linked by 3', 5'-phosphodiesters

•1957 Nobel Prize in Chemistry to Lord Alexander Todd "for his work on nucleotides and nucleotide co-enzymes" (nobelprize.org)

•Nucleotide sequence = DNA or RNA primary structure (compare protein primary structure)

OOP

O

O

O

O

O

OP

O

O

O

N

NN

N

NH2

N

NH

O

O

H3C

OOP

O

O

O

O

OP

O

O

O

N

NN

N NH2

H

O

N

N

NH2

O

5' end

3' end

DNA Carries the Genetic Code

Before 1944: Proteins believed to carry genetic information

DNA is not much more than a biological curiosity

1944: DNA demonstrated to be the cellular molecule that carries genetic information:

Avery, Macleod and McCarty: Studies on the Chemical Nature of the Substance

Inducing Transformation of Pneumococcal Types: Induction of Transformation by a

Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III, Journal of

Experimental Medicine, 1944, 79, 137-158.

After 1944: DNA is the hot topic in biology

Chargaff's Rules1950's: Erwin Chargaff studies heterocyclic base ratios in DNA from various organisms

Chargaff's Rules: In DNA of all organisms...

Species G A C T (G+A)/(C+T) A/T G/C

S. aureus 21.0 30.8 19.0 29.2 1.11 1.05 1.11

E. coli 24.9 26.0 25.2 23.9 1.08 1.09 0.99

Wheat germ 22.7 27.3 22.8 27.1 1.00 1.01 1.00

Bovine thymus 21.5 28.2 22.5 27.8 0.96 1.01 0.96

Human thymus 19.9 30.9 19.8 29.4 1.01 1.05 1.01

Human liver 19.5 30.3 19.9 30.3 0.98 1.00 0.98

•Base ratios random in RNA

•G/C ratio ~1:1

•A/T ratio ~1:1

•(G+A)/(C+T) = (purines)/(pyrimidines) ratio ~1:1

The Problem Solved1953:

} Not compatible with single helix

•James Watson and Francis Crick combine...Franklin's x-ray dataChargaff's rulesExamination of molecular models

} DNA is a base-paired double helix

•Rosalind Franklin: X-ray studies of DNA show helical structureDiameter = 20 ÅLength = 34 Å per 360o turnCalculated density

Watson and Crick made extensive use of models to study molecular structure. Follow their example!

Franklin's Photo 51. The X pattern is characteristic of a helical structure

= secondary structure of DNA

Watson-Crick Base Pairs

•Heterocyclic bases associate via two or three hydrogen bonds

Adenine-ThymineN

N

N

N

H N

N

N H O

deoxyriboseO

deoxyribose

H

CH3

Guanine-CytosineN

N

N

N

H N

N

HN

O H N

H

deoxyriboseO

H

deoxyribose

•Base pairs similar size and shape efficient packing into double helix

same size

Based-Paired Double Helix

DNA strands are antiparallel

Space-filling model: Atoms represented at their van der Waals radii (electron cloud volumes)

sugar-phosphatebackbone

minorgroove

majorgroove

360o turn

~10 base pairs

34

Pi stacking5' end 3' end

3' end 5' end

Hydrogen bondseasily disassembled

Strong

Based-Paired Double HelixPublication: Watson and Crick, Molecular Structure of Nucleic Acids: A Structure for

Deoxyribose Nucleic Acid, Nature 1953, 171, 737-738

"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."

"We have also been stimulated by a knowledge of the general nature of the unpublished experiment results and ideas of ... Dr. R. E. Franklin..."

1962 Nobel Prize in Physiology or Medicine: to Wilkins, Watson, and Crick "for their discoveries concerning the molecular structure of nuclear acids and its significance for information transfer in living material"

Optional reading: The Double Helix: A Personal Account of the Discovery of the

Structure of DNA (Watson)

The DNA Space Problem•Human genome = 3 x 109 base pairs (bp)•(3 x 109 bp) x (34 Å per 10 bp) x (10-10 m per Å) = ~1 meter in length

•Solution: DNA tertiary structure = supercoiling

Memorize DNA Structure?

CTGGAAGTACGTCTA

Leu LeuGlu Val Arg

LeuTTA TTG CTACTT CTC CTG

CTAGAAGTACGTCTT

Something

Something Alive

Something Alive (and complex!)

Origin of Universe

Origin of Life Variations

of Life

Nothing