►
From YouTube: Open Source Antibiotics Science Update Jan 15 2021
Description
Weekly open project meeting for Open Source Antibiotics Series 2.
Full Project: https://github.com/opensourceantibiotics/Series-2-Diarylimidazoles
Relevant GitHub Issue: https://github.com/opensourceantibiotics/Series-2-Diarylimidazoles/issues/51
On the call: Professor Matthew Todd, Dr Dana Klug, Giada Sabatino (UCL), Dr Chris Swain (Cambridge MedChem Consulting), Anthony Sama (citizen contributor), Lori Ferrins (Northeastern University)
A
Okay,
all
right
opens
up
anybody's
series
two
friday
january
15th.
I
was
just
saying
that
then
they're
recording
the
last
time
I've
uploaded.
Now
I
was
looking
back
through
it
because
there
were
an
awful
lot
of
really
good
suggestions
for
for
molecules,
and
I
started
to
try
to
capture
this,
but
I
just
run
out
of
time,
and
so
I'm
gonna
put
this
on
someone.
A
Is
that
all
right?
So
that's
the
meeting
yeah,
so
the
I
was
just.
I
went
through
the
yeah,
listen
to
the
meeting
again
and
there
were
a
huge
number
of
really
good
suggestions
here
from
everybody,
particularly
ones
where
we
were
talking
about
structures
that
we
could
make
as
feedstocks
to
allow.
You
know
diverse
syntheses
of
other
molecules
and
alternative
cores.
A
So
I
started
to
work
through
that
from
these
nodes
that
I
made
about
all
suggestions
which
we
have
captured,
but
you
know
are
presented
raw
and
we
need
to
prioritize,
and
so
I
started
sketching
up
a
few
of
them
there.
A
A
So
I
just
ran
out
of
time.
That's
all,
but
it's
it's
fun
to
do
this
in
terms
of
capturing
what
we
were
talking
about
believe.
B
It
or
not
for
the
for
quit
for
chris's
benzomidazole
hop.
I
actually
found
the
core
cheaper
at
sigma.
It's
20,
it's
24
quid
for
five
grams.
A
Okay,
great
great,
that's
the
kind
of
thing
that's
going
to
be
useful.
So
what
said
this
guy
here
sorry.
B
Yeah,
the
paradise
substitute
depends
on
middle.
They
were
doing
things
a
bit
differently.
They
were
using
some
sort
of
click
reaction.
They
tested
them
with
them
without
a
metal
insert
and
they
found
the
ones
without
the
metal
were
better.
I
couldn't
get
the
full
paper,
but
it's
on
the
wiki.
If
anyone
wants
to
try
and
log
in
with
their
credentials
great.
A
Great,
I
missed
that
if
you
could
just
link
that
here,
maybe
or
somewhere
just
so
we
got
it
all
together.
I
guess
I
missed
it
or
in
the
minutes
of
the
last
meeting
or
something
because
I
missed
it,
you've
done
that
all
right,
great
and
then
in
terms
of
the
shopping
list.
A
There
were
some
other
things
here
in
terms
of
if
we
wanted
to
try
and
explore
this
amino
substitution
that
we
were
talking
about
last
time
or
something
polar
that
I
wasn't
sure
so
danny
you
posted
that
very
nice
topless
analysis
that
you
did
and
the
suggestion
there
were.
I
I
don't
think
it
suggested
that
we
should
be
putting
things
like
amy's
in
that
position.
From
what
you
had
we
went.
You
were
trying
to
align
it
with
one
particular.
A
You
know:
sequence
in
the
topless
analysis
yeah,
but
I'm
not
sure
if
that
would
point
to
a
justification
of
putting
a
name
in
there
or,
if
or
if
we'd
be
going
against
our
own
analysis.
If
we
did
that.
A
E
A
A
E
C
A
Remember,
oh
sorry,
I
think
it
was
in
the
previous.
Wasn't
it
in
just
in
the
last
round,
I'm
forgetting
from
here.
D
A
But
I
don't
know
if
that
you
know
that
was
a
neat
idea.
I
guess
we
could
always
try
it
if
it's
simple,
but
I
wasn't
sure
if,
if
the
whole
point
of
your
analysis
doing,
it
was
to
say
don't
do
that.
B
Dimethylaminoboronic
acid
should
be
available
in
fluorochem
for
dimethylamino.
Phenylboronic
acid
should
be
there.
I
think
I
did
a
quick
supplier
search
on
the
bottom
of
that.
E
Yeah
I
mean
you
can
see
that
the
phenol
and
the
aniline
are
in
the
red
box,
which
so
yeah
I
kind
of-
am
wondering
if
maybe
it's
indicating
that
those
are
not.
A
F
Sorry,
I
just
wanted
to
ask:
can
you
actually
put
a
paradile
at
that
position
like
in
in
that,
where
the.
F
Yeah,
yes,
no,
but
I'm
asking
is
a
pyridine
tolerated
at
all
in
that
position,
because
I'm
wondering
if
you
could
actually
do
like
a
substituted
pyridine.
E
A
I'll
just
try
and
bring
that
up.
B
Mean
I
wonder
if
you
can
get
the
boronic
acid
of
three
nine,
just
a
nh
just
to
just
without
the
nh
put
a
boh
on
the
there
and
see
if
you
can
couple
that,
but
I'm
not
sure
if
you
can
get
that
fluoropyrite
in
boronic
acid,
it
could
be
pricey.
F
Yeah
I
mean
I
was
kind
of
thinking
about
actually
not
putting
it
at
the
four
positions.
I
think
we
we
said
that
the
like
a
fluoro
at
the
four
was
possibly
better
yeah.
That
was
I'm.
A
F
A
A
Okay,
all
right
great
we're
gonna
we're
gonna,
stick
that
on
the
list
right,
there's
a
specific
which
is
good.
Sorry,
I'm
just
trying
to
get
back
to
where
the
other
picture
was
so
just
I
think
the
other
thing
as
well
that
we
needed
to
fix
in
the
planning.
Besides
how
well,
besides,
you
know,
buying
some
of
the
starting
material
and
looking
at
whether
we
could
get
this,
which
was
the
other
call
that
you
suggested
laurie.
A
You
know
more
difficult,
less
of
a
feedstock
right,
but
whether
that's
accessible
from
starting
materials,
and
so
there
was
something
else,
but
I
forgot
is
the
shopping
list,
so
I
think
some
of
that
some
of
the
starting
materials
you
were
thinking
about
dana
for
the
for
the
one-pot
procedure
and
the
shopping
list
that
we
might
need
for
that,
were
you
were
you
able
to
order
some
stuff
or
have
I
did
I
miss
it?.
E
A
C
Did
we
ever
make
anything
with
you've
got
r2n
there
as
a
position
at
the
four
position,
but
what
about
making
it
put
a
ch2
n?
So
it's
actually
is
basic.
A
Yeah
and
this
the
stock
of
this
guy,
so
I
think
that
there
was
some
so
ed
was
just
done
the
scale
up
of
this
guy
for
the
stuff,
so
he
got
500
mix
or
something
of
this
guy,
and
so
he
wanted
to
play
with
chemistry
like,
for
example,
the
idea
that
chris
was
talking
about
with,
with
with
alkylating
the
nitrogen
and
reducing
this
generate.
A
And
then,
as
I
mentioned,
that
you
know,
there's
a
huge
amount
of,
let
me
just
close:
it
there's
a
huge
amount
of
other
stuff
in
here
which
we
were
mentioning
and
we
just
got
to
put
it
in
some.
You
know
order
list,
that's
all.
A
All
right
I
mean
the
other
things
here
are
just
fairly
quick.
I
guess
there's
been
no
chemistry
updates
because
of
course,
we've
been
away
and-
and
the
lab
is
still
closed-ish
at
the
moment
until
ed
and
danny
can
get
back
in.
So
we
haven't
got
a
lot
of
chemistry
stuff
to
do,
but
of
course
we
can
chase
the
cytotox
which
I'm
guessing
is
also
slightly
delayed,
but
we
can
keep
keep
asking.
E
I've
corresponded
with
them
and,
let's
see
so
I
emailed
renault
last
friday.
He
said
I'll
continue
working
on
your
compounds
next
week
when
alex
has
come
in
after
her
self-isolation,
so
they're
also
having
trophied
problems,
but
I
we
can
just
keep
it.
You
know
on
their
radar
and
I
think
they
are
planning
to
pick
it
up
soon.
Fine.
A
Okay,
awesome
and
just
there
was
just
this
note
about
the
talks,
data
on
on
your
compounds
laurie
and
what
we
learned
from
that
am
I
behind
the
times
there
is
this
already
done
or
have
we
just?
I
still
don't
remember
thinking
about
that.
A
Okay,
fine,
if
we
could
just
find
that
dig
it
out,
put
it
up
there
and
then
analyze
what
it
says.
That
would
be
helpful
and
then
the
hyphen
results
came
in
so
they've
been
busy
and
and
they've
they've
got
these
nice
results,
which
I
guess
is
I
mean
not
it's
not
it's
not
big
news.
A
Yet
it's
just
that
things
are
proceeding
according
to
plan
in
the
sense
that
they've
done
their
big
screen
and
they've
found
some
some
nice
results
that
give
them
a
decent
amount
of
a
pretty
pretty
simple
oxygenated,
mono
oxygenated
hydroxylate
vegetative
metabolite,
which
they
think
that
they
can
scale
up
and
and
send
us.
A
So
the
the
plan
is,
it
seems
like
quite
visible
this
month,
but
they
were
planning
to
do
this
in
february.
The
plan
is
that
they
are
going
to
do
that
scale
up
after
playing
around
with
a
few
different
conditions
and
and
send
us
the
crude
material
which
we
then
purify
and
characterize
by
nmr.
So
that's
the
deal
it's
they're,
gonna,
they're,
gonna
carry,
you
know,
carry
out
that
scale
up
for
us
and
then
we
do
everything
else
after
that
which
is
which
is
really
good.
A
So
I
mean
I
was
hoping
exactly
for
this,
that
they
found
something
that
was
looking
decent
and
should
allow
us
to
to
find
out
what
we've
got
two
monohydroxide
metabolites,
which
is
the
thing.
Those
are
the
things
that
we
get
through
from
then
that's
good.
I
mean
something
and
we'll
see
what
they
say.
Have
you.
F
Have
you
ever
looked
at
your
compounds
in
metasite.
E
A
Things
so
we
we
wait,
but
it's
good
that
they're
progressing
and
they're
still
active
in
the
lab,
which
is
correct
and
then
the
other
thing
which
is
the
I
guess.
The
main
item
for
us,
particularly
in
you
know
during
lockdown,
is
the
mechanism
of
action
stuff,
so
dana
posted
very
nice
analysis
of
which,
of
course,
I
can't
find
of
this
stuff
now,
which
I
will
pick
up
so
wait.
A
So
so
yeah
I
mean
just
so,
we
can
understand
experiment
the
data
dana.
Do
you
want
to
talk
us
through
this?
I
just
read
it
yeah.
E
Okay,
so
this
paper
that
I
pulled
this
image
from
is
lee
is
an
author
on
it,
and
so
it's
not
it's
sort
of
specific
to
the
experiment
that
they
were
doing,
but
I
think
the
same
experimental
design.
So
they
have
the
beads
that
which
are
so.
They
have
kinase
inhibitors
that
are
immobilized
on
the
beads.
So
that's
basically
the
solid
phase.
Then
they
either
incubate
the
mrsa
cells
with
dmso
or
our
compounds,
so
we
sent
them
an
activity
inactive
so
they
did
both
of
those
and
then
so.
E
So
if
you
see
decreased
binding
in
the
presence
of
compound,
then
that's
an
indication
that
your
compound
is
out
competing
whatever
the
inhibitor
is
on
the
bead.
That
would
be
pulling
down
the
the
protein,
but
that's
the
most
straightforward
way
to
interpret
the
results.
I
think,
and
so
then
the
data
that
they
sent
us
was
basically
a
list
of
proteins,
I'm
not
sure
whether
they're
all
kinases
or
not,
but
anyway,
and
then
they've
calculated
this
log2
fold
change.
So
it's
relative
to
dmso
for
the
active
compound
and
the
inactive
one.
E
Yeah
yeah,
so
it's
it's
basically
a
proteomics
sort
of
profiling
experiment,
so
the
ones
with
a
negative
fold
change
mean
that
the
protein
is,
I
don't
know
less
abundant
in
the
presence
of
compounds
and
then
a
positive,
full
change
means
that
it's
more
abundant.
So
there
were
quite
a
few
with
a
positive
full
change.
So
one
of
the
questions
that
I
have
for
them
would
be
like.
What
exactly
would
the
mechanism
be
so
where
your
compound
would
be
increasing
the
amount
of
protein
that
would
be
pulled
down?
I
mean
I
guess.
E
A
Yeah,
absolutely
so
what
I
was
going
to
suggest
is
that
I
ask
them
to
come
along
to
this
meeting
next
week.
A
E
Right
so
then
the
other
thing
I'm
not
clear
on.
I
think
that
these
would
these
are
mrsa
kinases,
but
we
need
to
know
how
they've
identified
them.
E
By
that
I
don't
know,
and
we
need
to
figure
out
whether
so
if
these
are
they're
human
kinases,
it's
going
to
be
a
bit
more
complicated
or
or
whether
they've
actually
gone
through
and
looked
at.
You
know,
what's
known
about
mrsa
and
the
kinases
that
it
expresses.
E
I
think
it
is
because
there's
a
sheet
in
their
excel
document
that
has
the
species
in
there,
but
so
I
I
mean
that
would
be
just
nice
to
get
that
confirmed
by
them.
So
we're
not,
you
know,
wondering
a
bit
and
then
I
think
we
need
to
find
out.
You
know,
what's
known
about
these
targets
and
whether
it's
reasonable
to
expect
that
that
would
be
the
mechanism.
A
I'm
just
I'm
just
thinking
about
whether
that's
true,
if
they're
all
yeah,
I
don't
know,
actually
I
don't
know
the
extent
to
which
these
are
immersive
versus
human
does.
Anyone
else
have
experience
with
this
slightly.
B
B
A
No,
no
sure
yeah,
I'm
just
I'm
trying
to
I'm
trying
to
work
out
from
the
experiment
whether
we're
talking
about
what
kind
of
targets
we're
talking
about
here.
That's
all.
B
A
E
G
I
don't,
I
think,
everything:
okay,
okay,.
A
Because
I
I
guess
I
I'm
just-
I
know
that
the
group
that
works
there
at
unc
is
has
a
huge
amount
of
expertise
on
human
kinases.
So,
yes,
I'm
just
thinking
how
it
is.
Maybe
it's
by
analogy
I
don't
know
so
I
think
that's
gonna,
be
our
first
question.
Isn't
it
to
make
sure
that
we're
dealing
with
those,
then,
of
course
the
question
is
well
all
right.
If
we're
talking
about
mercer
targets,
then
what
are
we
gonna?
A
Do
you
know
if
we
have
a
short
list
of
potentials
and
can
we
access
those
in
order
to
confirm
the
results.
H
H
Yeah
yeah,
maybe
some
verse
a
couple
of
these
proteins.
E
Right
well,
yeah,
that
if
we
went
through
and
found
out
whether
these
have
any
assigned
functions,
there
could
be
some
that
we
could
eliminate.
Based
on
that.
A
B
That
shouldn't
be
too
hard
to
do.
That's
a
quick
search
through
google
through
unifraud.
A
A
A
Yeah,
if
the
codes
tell
us
something
that
would
be
useful
sure
and
then
and
then
just
dump
it
somewhere.
That
would
be
useful.
B
A
All
right,
but
we
ain't,
so
I
think
we
we
we
can.
We
can
answer
all
these
things
next
week
when
we
get
one
we
we
have
the
you
know
the
team
themselves
on
speed
dial,
so
we
can
just
get
them
in
and
they
can
explain
the
whole
thing
which
is
really
good,
and
I
just
so.
I
think
it's
given
the
number
of
potential
proteins
in
that
spreadsheet.
The
fact
that
there
are
this
small
number
of
those
that
are
relevant
is
quite
good
news
at
the
outset,
I'm
saying,
ultimately,
you
know
experimentally.
A
Hopefully
we
can
whittle
it
down
even
more
but
great
that
it's
been
done.
I
don't
know
to
what
extent
they're
available
for
follow-up
experiments,
but
I
suspect
that
they
will
be
so
that's
good
all
right,
so
I
think
we'll
dominate
the
next
meeting
with
that.
A
All
right-
and
I
think
so
I
think
all
the
other
things
were
again
just
actions
for
people
to
deal
with.
The
only
thing
I
was
just
gonna
highlight,
I
think,
was
the
the
molecule
donations
terms.
I
tweaked
a
little
bit
whilst
I
was
thinking
about
it
over
the
break
and
if
they're,
okay,
because
I
didn't
change
anything-
I
just
sort
of
grouped
them
differently
to
try
and
make
them
a
little
bit
easier
to
understand.
A
So
there's
a
new
one
posted
here
a
week
and
a
half
ago,
where
I
just
tried
to
give
them
headings
and
try
to
group
them
together.
Then,
if
everyone's
okay
with
those,
then
those
just
need
to
go
on
to
the
form
that
you
know
that
you
had
already
generated.
A
Great
all
right,
that's
great,
but
nothing
new
there,
just
just
a
different
way
of
expressing
it
and
then
the
rest
of
it
was
as
as
perc
as
a
bunch
of
action
which
we
haven't
done.
You
know
christmas
is
one
of
those
times
when
you
get
done
far
less
than
you
think
you're
gonna
get
done
even
in
a
long
day
on
christmas,
I
didn't
get
all
these
things
done.
So
was
there
anything
else?
Anyone
was
thinking
about
or
wanted
to
talk
about
before
we
wrap
up.
B
It's
on
the
wiki.
It's
in
related
compounds.
A
Oh,
this
guy
I
may
have
to
just
if
everyone
can
talk
amongst
themselves.
I
can
probably
do
this.
Well,
actually,
you
know
what
we
can
do
this
offline.
What
we
might
be
able
to
do
is
is
share
it
around
us
a
little
bit
and
then
have
a
think
about
it,
rather
than
you
yeah
watching
me
entertainingly
log
in
through
ecl's,
but
that's
great
you've
done
that.
So
that's
a
that's
an
item
we
can.
We
can
look
at
and
think
about
the
next
time,
just
conscious
people's
time.
A
Yeah
all
right
great
so
next
week
we'll
focus
on
the
other
stuff,
but
until
then
it
does
nothing
else
have
a
great
week.
Thanks
for
coming.