Transcript Origin of Chirality in Proteins

Possible Origin of Chirality in
Proteins
Malcolm E. Schrader
Institute of Chemistry
The Hebrew University of Jerusalem
ILASOL 27
DECEMBER 1, 2013
The Weizmann Institute of
Science
Chromatographic column
hypothesis
• In today’s talk I review previous, and
explore additional, consequences of
my approach claiming that prebiotic
small atmospheric molecules
concentrated and reacted, in a quasichromatographic column, on land
rather than in the oceans.
Mainline Approach to Chemical
Evolution on Earth: Oparin
1. Atmosphere at time of origin of chemical
evolution was reducing
2. Molecules from reducing atmosphere
dissolved in oceans.
3.Under energetic activation they
ultimately polymerized to biological
polymers.
UREY
Continued postulate of reducing atmosphere from his
own model of planet Earth formation.
a. Slowly cooling planet
b. Presence of iron in crust removed oxygen from
atmosphere
c. “Atmosphere mainly”:
H2, CH4, N2, NH3
d. “Smaller amounts”:
CO2, CO
ATMOSPHERIC COMPOSITION REVISITED
1. Earth cooled fast
2. Iron core formed fast
3. Thus removing an important oxygen getter from
contact with atmosphere.
4. Newly favored atmospheric composition:
N2, CO2, H20,
and H2, CO in small amounts.
Possible results
• Pinto et al showed that HCHO could be
produced from this nearly neutral atmosphere.
• Zahnle showed that if CH4 were also part of this
atmosphere, HCN could be produced. However,
he pointed out, CH4 could not be part of the
model of this nearly neutral atmosphere
• We pointed out that prebiotic CH4, however, was
still being emitted in local spots.
RNA OLIGOMER UNIT
Ferris, 2004
Cyanomethanol Hypothesis
HCN mixes with similarly deposited formaldehyde
from raindrops
HCN + HCHO → CH2(CN)OH
5CH2(CN)OH → adenosine + H2O
This provides explanation for pentose
(rather than hexose) inclusion in RNA/DNA
Schrader, M. E. (2009) J. Geophys. Res. 114, D15305
Polypeptide (Protein Backbone)
from Cyanomethanol. 1
•
H
H
H
• NΞC─C─OH + NΞC─C─OH + NΞC─C─OH
•
H
H
H
•
↓
↓↓↓
•
H
H
H
• NΞC─C─C ─ N ─C ─ C ─ N ─ C ─ OH
•
H ║ H H ║ H H
•
O
O
Polypeptide (Protein Backbone)
from Cyanomethanol. 2
•
H
H
H
• NΞC─C─OH NΞC─C─OH NΞC─C─OH
•
H
H
H
•
↓
↓↓↓
•
H
H
H
• NΞC─C─N ─ C ─C ─ N ─ C ─ C ─ OH
•
H H ║ H H ║ H
•
O
O
Enthalpy (kcal/mole)1.
•
•
•
•
•
•
•
break
C ─ OH
C≡N
CH2 ─ OH
N≡C ─ CH2
90
212.6
101.5
95.3
make
CH2 ─ CO
CO ─ NH
NH ─ CH2
C=O
N─H
amide resonance
72
72.8
72.8
176
98.8
20
•
• Total
499.4
512.4
Enthalpy (kcal per mole) 2.
• Breaking energy
Forming energy
• H2C ─ OH
90
• N ≡ C─CH2
212.6
• CH2O ─ H
101.5
•
•
•
• Total
O ═ C
O═C ─ NH
N ─ H
H2C ─ NH
176
72.8
98.8
72.8
amide resonance 20
404.1
Total
429.4
Likely mechanism
• It can be seen that stronger bonds must
be broken in mechnism 1 over mech 2.
While thermodynamically the difference
between making and breaking bonds
should be the same in each case, the
larger values in mechanism 1 imply a
greater activation energy.
• We therefore assume mechanism 2 to be
correct in all cases.
Chromatographic Approach and
Chirality
• The foregoing approach can lead to
complete chirality in proteins.
• To understand how, we first review
the presently accepted chemical
origin of proteins
Chirality in Proteins
• Chirality. The conventional approach to
chirality in proteins is based on the
assumption that proteins were originally
built up from the hydrolyzed segments that
we now obtain, and assumes that they
were formed by the condensation of these
amino acid segments.
Conventional Approach
• Nearly every one of these amino acids
obtained from protein hydrolysis has an
alpha carbon atom of the same chirality,
called levo for this case of proteins. Thus,
in the condensation written below, any
amino acid, RCHNH2COOH, where R is
any organic group found in amino acids,
will react with another amino acid, where
R may be the same or different for each
segment, to form a protein, as follows:
Conventional Approach
•
R
O
O
O
•
│
║
H ║
H ║
• HN – Cα – C – OH + HN – Cα – C – OH + HN – Cα – C – OH
•
H H
H
│
H
│
•
R’
R’’
•
↓
[5]
•
R
O
O
O
•
│
║
H ║
H
║
• HN – Cα – C – N − Cα – C – N - Cα – C – OH + 2H2O
• H
H
H │
H │
•
R’
R’’
Conventional Approach
• Thus, from this point of view, it is a
mystery why the Cα groups in the
backbone of the resulting proteins, are all
of the same chirality. For example, if we
take the first amino acid on the left as levo,
then the other two can be dextro, as
indicated, and the succeeding amino acids
may also be one or the other. There is no
reason why all the monomers (aminoacids) should be either d or l exclusively.
Peptide/polypeptide adsorption
• If the peptide and polypeptide are formed
from an adsorbed monomer, without
including any R groups, the situation
changes.
Adsorption to solid surface
• It is a basic tenate of our approach that the
prebiotic oligomers and polymers were
formed by monomers flowing through or
on mineral surfaces which act as a quasichromatographic column. Thus they may
be regarded as having been essentially
adsorbed to a solid surface.
Adsorption 2.
• Adsorption of even small molecules are now
known to often adsorb in the form of
separate islands.
• This phenomenon has now become
popularly described as “self assembly”.
• Of course, what is really governing the
phenomenon is free energy of adsorption.
• Molecules from the environment adsorb and
desorb in amounts governed by the negative
free energy of adsorption. Considering that
alone, no islands are formed.
Adsorption 3.
• However, adding to the free energy of
adsorption of individual molecules, there is
possibility of attractive lateral interaction
between adsorbed molecules, thus islands
may be formed.
• This essentially two dimensional product
suggests, intuitively, due to the spatial
restriction, a possible cause of chirality.
Recent mineral studies
• There has recently been a commendable rash of
speculation on the possibility of chirality in
mineral surfaces forcing chirality on adsorbed
amino acids.
• (This approach is usually combined with the
classical “soup” assumption of origin of life
speculation, so that the soup somehow comes in
contact with the minerals. By contast, our
approach involves a land based phenom, with
water, possibly rain, as eluent.)
Two dimensions
• At any rate our approach here differs from
those attempts in that we focus solely on
the dimensionality of the adsorbing polar
surface, without assuming it to have any
intrinsic chiral properties.
Cyanomethanol adsorption 1.
• We now examine the approximate nature of the
adsorption of cyanomethanol, our hypothesized
monomer, to a two dimensional polar surface.
• The monomer is a tetragon, a triangle of which
rests on a surface with a group or atom in each
of the 3 corners of the triangle and a fourth
corner perpendicular to plane of surface. A
carbon atom is in the middle above plane of
surface..
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27
Adsorbed cyanomethanol
H
c
N≡C
OH
Adsorbed cyanomethanol
H
H
c
N≡C
OH
Cyanomethanol adsorption 2.
• Since the surface is polar, both the CN
and OH groups must be in the triangle
adsorbed to the surface. Thus, the third
corner is occupied by an H atom, and the
other H atom is perpendicular to surface.
• In terms of future reaction, then, one H is
on surface relatively inaccessible, while
the other protrudes and is very accessible.
Cyanomethanol adsorption 3.
• Therefore, due to two dimensional
confinement of the molecule on the
surface. the two hydrogens are no longer
equivalent
• The adsorbed cyanomethanol monomer is
then here called quasi-chiral.
2-dimensional polymerization
• In order for the CM molecules to
polymerize in a straight line as pictured, a l
molecule as pictured, could be next to
another l molcule, as pictured, since the
CN group requires an OH for reaction.
2-dimensional polymerization of CM
•
C
≡
N
H
H
C
C
N≡C
O
H
O
H
enantiomers
•
•
N≡C
O
H
O
H
C
≡
N
Possible reaction
• The 2 enantiomers as pictured cannot
react along a straight line
• However, if a d group near the l is rotated,
in the plane, there can indeed be reaction,
which can be propagated in 2 dimensions
regardless of l or d chirality.
• So, two dimentional confinement is not
sufficient to force pure l (or d)
polymerization.
Enantiomers.2
•
•
OH
H
N≡C
O
H
C
N
One dimensional adsorption
• Now, consider a partially opened book.
• The interface between the two exposed
pages now consists of a more or less one
dimensional space in which small
particles can comfortably nest.
• Transform the picture to a nano sized
crevice in a mineral surface.
Adsorption in crevice
H
NC
H
OH
NC
OH
One dimensional adsorption of
cyanomethanol
• The two polar groups will now adsorb to
the bottom of a crevice where they each
interact with two surfaces at once.
• The H of the triangle containing the
adsorbed polar groups is now assumed to
lean back to one of the joined surfaces
which form the crevice.
One-d adsorption
• The other surface forming the crevice is
short, and the H perpendicular to the
triangle protrudes and is available for
reaction.
• Ultimately, R groups of various types
replace the protruding H’s and the alpha
carbons all remain completely levo (or
dextro).
Glycine condensation
• The same considerations may be applied
to the conventional proposed
condensation mechanism of prebiotic
polypeptide/protein formation provided that
the monomer is glycine and the
condensation takes place in a onedimensional crevice on a quasichromatographic land-based column
which removes the H2O product.
Quasi-chirality from adsorbed glycine
•
O
O
O
•
H ║
H ║
H ║
• HN – Cα – C – OH + HN – Cα – C – OH + HN – Cα – C – OH
•
H H
H H
H
H
•
•
↓
[5]
•
O
O
O
•
H
║
H ║
H
║
• HN – Cα – C – N − Cα – C – N - Cα – C – OH + 2H2O
•
H H
H H
H H
•
Conclusions 1.
• Replacement of the conventional water
based “soup” approach to prebiotic
polymerization, with the the land-based
“chromatographic column” approach, results
in possibilities for complete chirality of
proteins.
• Specifically, the monomer, preferably
cyanomethanol, can adsorb and react in a
largely one-dimensional crevice to form a
completely l (or d) chiral protein.
Conclusions 2.
• Many factors must fall into place,
spatially and temporaly, for the process
to succeed.
• A low probability may therefore have to
be assigned to the occurrence of
chemical evolution on the planet Earth.
• Does this support or detract from the
theory?
Acknowledgment
• The author thanks Shmuel Yariv and
Yitzhak Lapides for their valuable
comments.
•
• Thank you for your interest!!