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From YouTube: Open Source Antibiotics Science Update Jul 24 2020
Description
First of (what should be) weekly science updates related to Open Source Antibiotics Series 2. Full project: https://github.com/opensourceantibiotics/Series-2-Diarylimidazoles. Relevant page: https://github.com/opensourceantibiotics/Series-2-Diarylimidazoles/issues/19. On the call: Professor Matthew Todd, Dr Dana Klug, Dr Edwin Tse (all University College London), Dr Alvaro Lorente (Edinburgh) and Antony Sama.
B
A
Great
okay,
all
right
welcome
everybody.
This
is
open
source
antibiotics
series,
2,
update
meeting
for
everyone
to
connect
and
and
talk
about
what's
currently
going
on.
So
I'm
just
going
to
go
back
to
the
previous
meetings
notes
so
that
we
can
run
through
things
quickly
and
just
update
ourselves
on
what
we've
got
to
do
so
this
last
time
we
met,
we
talked
about
it's,
not
warm.
It's
just
about
community
updates.
A
A
way
of
you
know
making
sure
that
people
in
the
community
know
what
we're
doing
useful
to
be
able
to
do
that
to
you
know,
send
out
little
messages
and
tweets
and
and
make
little
tiny,
25
second
videos
or
something,
and
that
still
stands.
I
think
it's
still
important
that
we
do
that.
If
anyone
is
doing
some
work
for
the
project
or
wants
to,
you
know
tell
people
what
they're
doing.
I
think
it's
a
good
way
of
doing
things
so
that
kind
of
can
remain
there.
A
The
second
one
was
about
lab
books.
I
think
ed
you've
added
your
lab
book
to
the
wiki
yeah
great.
So
we
can.
We
can
delete
that
because
I
think
the
relevant
lab
books
are
done
alvaro.
This
is
just
about.
You
know
we
use
these
electronic
lab
notebooks
and
we
can
make
them
public
and
it's
important
that
they're
listed
there
if
you
ever
do
anything
like
that
or
have
an
electronic
lab.
A
No,
but
where
you
can
share
things
and
that's
great,
but
obviously
dana
and
ed
are
doing
the
chemistry
so
they're,
starting
to
pile
up
the
the
results
and
experiments
and
data
that,
but
that
just
means
that
everyone
can
see
what's
going
on
all
right,
good,
so
number
three
was
we're
awaiting
confirmation
that
relevant
samples
for
this
project
are
still
in
the
fridge
at
university
of
north
carolina
chapel
hill,
and
I
pinged
the
team
back
there
just
yesterday
again,
and
I
think
that
we
just
had
a
reply
from
caro
to
say
that
all
of
the
compounds
that
we
wanted,
which
is
great
so
the
there-
was
an
error
dana
in
that
email
about
one
of
the
codes.
B
A
Thanks,
that's
great
now,
the
so
so
the
the
compounds
that
we
really
wanted
were
the
ones
that
we
were
shipping
to
monash,
for
evaluation,
for
physical
chemical
properties
and
in
vitro
clearance.
I
think
so.
I
got
all
the
information
from
the
monash
team,
which
is
great,
so
the
the
compounds
can
be
sent
to
karen
white.
The
unc
team
have
to
do
a
bunch
of
paperwork
for
that
which
is
fine.
They
did.
A
A
But
that's
on
me,
which
is
fine,
so
monash
can
do
the
analysis.
They've
got
a
bit
of
a
backlog,
but
they
can
do
it
and
carrow
is
willing
to
send
and
has
has
money
to
do
that.
So
that's
part
of
the
ground,
so
that's
good,
so
we
can
get
those
scent.
The
number
of
molecules
is
about
four
or
five
or
something
so
when
we
make
more,
we
can
have.
Maybe
you
know
two
more
rounds
of
two
or
something
because
we
have
money
for
nine
and
then
right
at
the
end
of
the
project.
A
We
have
money
for,
for
some
in
vivo
work
for
one
compound
that
we
like
the
most
that's
how
much
money
we've
got
so
everything
else
we'd
have
to
ask
for
favors,
but
that's
it.
Hopefully
that's
that's
enough
all
right!
So
that's
obviously
gonna
be
pretty
crucial
because
fixing
things
the
the
clearance
was
obviously
a
key
priority
for
this
whole
thing.
A
That
also
covers
five
issue:
five
about
the
in
vitro
pk.
So
that's
that's
all
going
ahead,
which
is
great,
I
think
it's
up
to
those
two
teams
now
to
to
get
the
compounds
shipped
just
going
back
to
four
on
the
mechanism
of
action
stuff
there.
So
the
idea
is
that
the
lee
graves
and
team
at
unc
are
going
to
be
doing
some
of
the
experiments
to
try
and
work
out
how
these
compounds
work
and
they're
happy
to
do
that.
A
Two
different
techniques
that
are
linked
to
in
in
item
15
now
issue
15..
He
asked
this
question.
I
don't
know
if
this
means
anything
to
you
alvaro,
but
he
has
this
question
about.
What's
the
base
cell
type
for
the
experiments,
does
that
mean
anything
to
you.
C
A
But
he's
doing
he's
doing
mechanism
of
action,
so
he's
he's
trying
to
fish
out
a
target
and
I'm
just
trying
to
work
out
what
that
what
base
cell
type
means.
But
I
can,
I
can
ping
him
again.
A
On
that
right,
I
had
a
really
good
conversation
with
him
when
I
was
there
with
lee
about
the
experiments-
and
it
looks
really
interesting,
but
he
never
covered
that
so
either
I
wait
for
his
email
or
I
try
and
read
some
of
his
papers.
It's
going
to
be
quicker
to
wait
for
the
email
response.
A
Okay,
number
six
was
about
the
screening
all
right,
so
this
is.
This
is
an
interesting
one.
We
will,
you
know,
need
periodic
and
ideally
small
numbers,
every
now
and
again
of
screening
for
potency
against
mrsa
and
for
any
actives,
and
maybe
the
occasional
inactive
screening
for
mammalian
cellular
toxicity.
A
Just
to
check
that
we've
we've
got
potency
and
we've
got
selectivity
now
this
can
be
done
internally.
It's
a
little
difficult
because
of
the
of
the
lockdown
stuff.
That's
going
on
at
the
moment
that
some
parts
of
the
building
aren't
up
and
running
yet,
and
this
kind
of
screen
is
not
running
all
the
time.
A
So
I'm
in
touch
with
both
paul
stapleton,
a
colleague
of
mine,
he's
able
to
do
the
mrsa
and
andreas
who's
able
to
do
the
talk
screening
and
I'm
trying
to
work
out.
You
know
the
capacity
they
have.
I
did
also
this
morning
go
back
and
check
the.
What
co-op
can
do
the
queensland
guys,
what
they
can
do
and
and
mrsa
is
one
of
their
pathogens
that
they
screen
against,
and-
and
I
know
that
you
know
for
compounds
that
here
they
do.
They
do
also
do
generic
mammalian
toxicity
assays.
A
I'm
not
quite
sure
the
state
is
occurred
at
the
moment,
so
I've
emailed
mark
blaskovich,
who
runs
that
and
to
see
if
they
could
take
some
of
those
compounds.
The
huge
disadvantage
of
that,
obviously,
is
that
they
are
in
australia
and
we're
not
in
australia,
anymore,
we're
in
london.
So
it's
going
to
take
a
while,
whereas
of
course
you
know
paul
is
in
the
same
building
and
it'll
be
very
convenient,
but
I'll
see
what
comes
back
from
that
coad
also.
A
A
If
anything,
if
any
other
suggestion
the
solutions
come
to
mind
for
that
any
other
possibilities,
then
then
let
us
know.
As
far
as
I
remember
dana
I
haven't
looked
at
this
for
a
while,
but
I'm
pretty
sure
that
in
the
proposal
we
mentioned
that
the
data
suggests
that
mrsa
is
the
only
organism.
D
Yeah
they're
not
active
against
the
other
pathogens,
no
yeah,
so.
D
A
Yeah,
okay,
all
right,
fine,
all
right.
So
that
brings
us
to
synthetic
chemistry.
Now,
we've
only
just
started
this
obviously,
but
did
you
guys
want
to
share
a
slide
or
anything
yeah?
I've
got
a
slide.
I
can
I'll
get
off
the
show
yeah.
A
D
Sure
so
ed-
and
I
both
made
this
the
cyclization
product
and
neither
of
us
are
getting
great
yields.
D
I've
actually
done
this
reaction
twice
and
I
ran
a
2d
tlc
on
the
crude
material
from
the
when
I
did
it
the
second
time
and
it
looks
a
bit
messy,
so
I
might
try
to
just
push
it
to
the
bromination
and
then
purify,
and
then
the
bromination
we've
ed
and
I
have
both
tried.
It
works
fine.
I
did
try
to
do
the
borrelation
last
night.
I
don't
think
it's
worked,
but
we
don't
have
anhydrous
dioxane
in
the
lab,
which
is
a
solvent
that
you
really
should
be
using.
D
C
Yeah,
well,
the
I
I
did
the
I
I
didn't
make
the
boroni
esther,
because
I
use
it
as
a
with
the
bromine
and
then
I
do
the
suzuki
using
different
boronic
ester
or
boronic
acids
yeah.
But
it
is
true
that
the
first
step
it
was
it
was
very
low.
The
yields
for
for
some
of
the
cores.
I
don't
know
why
I
tried
to
modify
the
base
the
equivalent
of
base.
C
I
think
I
also
tried
different
solvents
in
dioxin
or
thf,
but
dmf
was
the
the
better
because
of
the
solubility
of
the
reagents,
because
both
are
salt
in
this
case
and
the
first
step
is
it's
an
issue,
but
you
can
continue
if
you
don't
need
to
make
a
lot
of
deliberatives
in
the
final
step.
I
don't
know,
did
you
purify?
Would
you
always
purify
the
intermediate,
or
did
you.
C
In
the
first
step,
I
use
a
chromatography
column,
flash
chromatographical
method,
the
second
one-
I
don't
remember,
I
think
I
yeah-
I
also
use
the
chromatography
and
for
the
final
coupling
I,
the
compounds
were
very
polar,
so
we
didn't
have
the
the
like.
The
sorry.
Well,
the
chromatography.
I
I
don't
remember
the
name,
the
chromatography
machine,
to
purify
that
using
reverb
phase
chromatography.
C
C
A
A
C
C
The
deal
were
almost
the
same
and
also
I
checked
the
papers.
Well,
the
the
first
paper
where
they
reported
these
compounds.
They
purified
the
final
compounds
using
the
reverse
chromatography,
but
the
first
step
for
the
first
step.
They
use
a
different
core
if
you
have
seen
the
well
ordered
derivatives
for
other
main
course,
the
yield
were
much
higher,
maybe
60
70
percent,
but
for
this
exactly
one
it
was,
I
don't
remember,
but
maybe
20
percent
or
something
similar.
F
A
A
D
D
Yeah,
it's
it's
a
bit
messy.
A
And
sorry
so
just
remind
me,
though,
the
one
that's
being
so
the
middle
compound
at
the
bottom,
that's
the
active
or
the
inactive.
I
forget
sorry.
D
F
I
did
notice
something
interesting
regarding
possible
metabolic
stability.
There
was
a
parrot,
the
methyl
thioether
that
was
that
had
four
potency
in
the
screen.
So
what
if
we
make
the
sulfoxide
on
that
the
cell
phone
rather.
F
Listed
it
on
the
suggest,
I
don't
know
if
I
can
share
my
script,
I
don't
know
how
to
share
screen,
but
I
had
I
pushed
everything
just
two
days
ago.
Oh,
that
was
the
push
right.
It
was
something
very
interesting.
I
noticed
about
one
of
the
compounds
that
if
it
is
potent
it
would
be
basically
rock
stable,
so
it
could
be
a
way
out,
because
that
thiopeen
ring
is
probably
just
getting
shredded.
A
Yeah,
so
just
on
that
wait
a
minute,
let
me
just
bring
that
up.
A
All
right,
I
think,
but
that's
all
in
the
chemistry
right,
because
we
we
we'll
wait
and
see
what
happens.
I
guess
with
the
with
that.
It's
only
been
a
few
days.
Let
me
share.
A
A
So
yeah
so
just
coming
back
to
things
here,
so
I
think
we've
got
yeah.
That's
the
synthetic
chemistry
dealt
with
the
compound
numbering.
I
mean
as
you're.
Making
these
things
just
make
sure
that,
in
addition
to
your
codes,
you
have
the
osa
number,
because
then
they
all
collapse
into
one
number
and
with
different
batch
codes,
the
yeah,
so
the
metabolic
transformation
thing
and
isolating
metabolites
so
that
yeah
that's
interesting.
A
So
our
previous
collaborator,
scott
on
open
source,
malaria,
scott
obeck,
is
happy
to
have
a
go
at
this
and
to
for
us
to
send
some
compounds
to
him
when
he,
when
we
have
them
so
that
we
can
see
what
the
metabolites
are
and
that
will
give
us
some
clues
very
useful
and
important.
I
think,
and
also
we
can
isolate
the
metabolites
and
get
them
evaluated
for
potency
in
case.
In
fact,
it's
a
metabolite
that
is
the
active
compound.
A
He's
also
done
a
very
nice
thing
for
us
and
he's
introduced
us
to
a
uk
company.
Who
does
this
kind
of
work
also
to
see
if
they
may
be
interested
in
contributing
to
the
project?
A
company
called
haifa
and
I
saw
a
poster
from
them
a
while
back
with
some
really
nice
work
that
were
similar,
and
I
thought
maybe
we
could
do
something
with
them.
The
only
advantage,
of
course,
is
that
they
not
the
only
advantage.
A
An
advantage,
of
course,
is
that
they're
in
the
same
country,
so
it
might
be
easy
to
send
compounds
and
stuff,
but
I'll,
follow
it
up
and
see.
If
they're
interested
in
in
working
on
this
either
way,
scott's
happy
to
do
some
testing,
which
is
good,
I'm
pretty
sure
that
we
don't
know
what
the
metabolites
are.
But
I'd
put
it.
Would
it
be
too
out
of
out
of
range
to
predict
that
that
thy
opinion
is
getting
shredded
yeah
I
mean
it's
likely
for
sure
and
that's
the
prediction.
F
But
I
did
have
a
couple
proposed
compounds:
if
anyone
wants
to
take
them
off
just
for
ideas,
I
had
improving
water
solubility
metabolic
liability.
A
Yeah,
I
think
once
we
once
we're
familiar
with
the
chemistry
we
can
start
messing
around
so
once
we
end
on
that.
That
comes
to
that
that
point
11,
just
as
a
reminder
that
when
we,
when
we
do
design
you
know
molecules,
then
we
just
keep
an
eye
on
log
p,
predict
it
and
and
keep
on
doing
these
smart
type
calculations,
because
that
would
be
useful
as
a
to
ensure
that
we're
not
introducing
things
that
are
that
are
liabilities.
A
A
On
the
just
on
the
the
other
issue
about
so
this
series
came
from
a
group
at
gsk
in
north
carolina.
That's
the
that's
how
it's
happened.
You
know
it
was
being
looked
at
internally
in
gsk
for
something
and
then
some
of
the
molecules
went
over
to
some
of
the
screening
sets
at
in
in
academic,
north
carolina,
chapel
hill
and
then
the
this
is
where
these
molecules
came
from.
A
So
we
are
now
finally,
through
some
kind
emails
from
the
unc
guys
we're
in
touch
with
the
corresponding
author
on
the
original
paper
from
gsk
that
found
these
compounds,
and
so
we
have
teleconference
lined
up
next
week
to
talk
about
what
they
might
be
able
to
tell
us
and
what
they
have
to
hand.
A
Obviously,
samples
of
molecules
would
be
great,
but
even
more
usefully,
maybe
would
be
if
they
had
done
internally
on
their
projects.
Some
of
this
metabolic
clearance
stuff
and
found
the
answer
already,
but
maybe
because
the
series
was
killed,
it
never
reached
the
light
of
day.
So
that's
going
to
be
the
key
part
of
that
conversation.
I
don't
know
yet
what
we're
going
to
be
allowed
to
share.
A
A
Do
they
know?
Why
do
we
know
why
they
were
a
cam?
No,
no,
and
we
may
not
ever
know
so,
we'll
see
what
we'll
see
what
we're
told,
but
always
great.
To
I
mean
it's
really
good.
Often,
of
course
you
know
you
go
back
to
projects
that
have
been
reported
a
few
years
ago
and
people
have
left
or
moved
on
or
whatever,
and
you
can't
get
back,
but
it
looks
like
we're
in
touch
with
both
the
people
who
are
doing
the
discovery
and
the
development
of
the
compound.
A
So
that's
great
and
they're
both
available
on
the
webex.
So
hopefully
we'll
get
something
useful
out
of
that,
and
then
the
only
last
point
I
think,
was
if
we
down
the
line,
if
we
wanted
to
try
a
sort
of
higher
throughput
quick
test
for
metabolic
liability,
some
sort
of
in
vitro
test
which
doesn't
involve
enzymatic
transformations,
but
something
chemical.
Whether
we
could
use
anything
you
know
sort
of
chemical
reagent
to
assess
metabolic
clearance
dana.
You
did
some
searching
on
this.
I'm
sorry!
If
you
have
already
posted
about
it,.
D
Yes,
I
did
so.
I
just
have
sort
of
a
summary
of
things
that
I
found
in
a
google
doc,
but
I
guess
the
most
relevant
thing
that
I
found
was
people
looking
at
using
porphyrins
to
be
like
sort
of
enzyme
mimics.
D
It
seemed
like
a
bit
of
a
specialized
system
and
then
I
don't
know
to
what
extent
it's
been
validated
as
like,
actually
mimicking.
A
A
D
F
Yeah
I
couldn't
find
anything
either.
I
was
searching
on
a
company
called
porphichem,
which
is
supposedly
a
world
expert
in
warfarin.
Looking
for
a
catalyst
for,
I
believe,
osm
series.
Three,
you
know
there
was
an
issue
there
with
one
of
the
palladium
complexes,
not
working.
I
mentioned
this
briefly
to
thaw
and
yeah.
They
just
sell
them
one
by
one.
They
don't
sell
cocktails
for
anything.
A
Okay,
all
right,
that's
fine!
I
mean
it
would
be
such
a
first
pass
thing.
I
was
thinking
of
something
where
you
know
you
could
just
sort
of
chuck
some
in
then
by
tlc.
You
know
or
lcms
watch
disappearance
of
compound
and
if
it,
if
it
behaved
well
on,
if
there
was
a
correlation
between
what
we
knew
from
the
monash
work
and
that
we
we
might
then
be
able
to
do
a
sort
of
higher
throughput
analysis
of
potentials.
A
But
it's
okay.
If
it
doesn't
exist.
A
Yeah
yeah,
the
analytical
and
the
and
the
prep.
C
C
Also,
you
need
to
run
the
the
column,
but
with
the
three
iteration
you
will
have
your
compound
quite
few
more
than
95
98
and
I
found
that
this
solving
mystery
is
the
the
perfect
one.
C
So
I
I
don't
know
exactly
which
one
was
purified,
but
if
you
look
in
the
in
the
document,
I
send
you
not
in
the
general
procedure
but
under
like
I
have
here,
for
example,
this
was
for
the
compound
alm
d8i20
and
when
you
see
the
yield
you
will
see
if
I've
used
the
tritium
relation
or
not.
But
this
is
a
key.
A
A
A
We
love
automation,
so
we've
got
the
biocharge
right
next
to
the
lcms.
Okay,
so
we're
okay,
but
that
yeah,
it's
even
faster.
If
you
can
situate
or
crystallize.
A
A
If
not,
then
that's
great
thanks
for
coming
along
thanks
a
lot
for
coming
on
guys,
that's
really
helpful
and
hopefully
see
you
at
a
future
weekly
update
meeting
cool
great
thanks
for
coming
along.
Thank
you
all
soon,
bye.